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Fanconi-Bickel syndrome (FBS) is a rare genetic disorder of carbohydrate metabolism due to pathogenic variants in SLC2A2, a gene encoding glucose transporter 2 (GLUT2), which leads to accumulation of glycogen in the kidney and liver. While consequential complex proximal tubular dysfunction is well acknowledged in the literature, long-term trajectories of kidney function in patients with FBS have not been well characterized, and kidney biopsy is performed infrequently. Here, we report on a patient with FBS followed from infancy through young adulthood who presented early on with hypercalciuria, phosphaturia, and hypophosphatemia, complicated by chronic kidney disease development during childhood. Kidney biopsy, in addition to a widespread glycogen accumulation in proximal tubular epithelial cells, demonstrated medullary nephrocalcinosis. Screening for nephrocalcinosis may be warranted in pediatric patients with FBS, along with close surveillance of their kidney function. [ABSTRACT FROM AUTHOR]

Both the quality of chicken meat and the quality of chicks are influenced by the level of breast muscle glycogen reserves. In order to study the role of digestive metabolism in establishing this muscular phenotype, we compared two divergent chicken lines for the ultimate pH (pHu) of the breast meat, a proxy for glycogen reserves. Males aged 4 weeks had twice the breast muscle glycogen content in the pHu- line (low pHu) than in the pHu + line (high pHu). The increase in glycogen reserves (pHu-) was associated with a higher relative weight of the proventriculus and gizzard, as well as better apparent ileal digestibility of nitrogen and calcium. The diversity of the cecal microbiota was comparable, but three bacterial genera (Lachnospira, Lachnospiraceae UCG-010, Caproiciproducens) varied between the lines. The differences observed could lead to down-regulation of carbon fixation in prokaryotes and of the citrate cycle in the pHu + line. RNA-seq analysis of the jejunum, the major site of nutrient absorption, revealed 149 genes differentially expressed (DE) between the lines, including several genes linked to immunity, hormonal response and circadian rhythms that are less expressed in pHu + animals. Others involved in cell migration and proliferation, and more generally tissue morphogenesis, also differed between the lines. Among the DE genes, several co-localized with Quantitative Trait Loci (QTL) controlling pHu and selection signatures identified in the divergent lines, such as the gene coding for ghrelin, a hormone regulating appetite. [ABSTRACT FROM AUTHOR]

To investigate the effect of Tetrasphaera's enrichment on phosphorus removal mechanism, three micro-pressure swirl reactor (MPSR) groups were used to experiment on sewage treatment under different SRT (17.2, 50.8, and 68.2 d). Results showed that Tetrasphaera enrichment in the MPSR system was promoted by extending the SRT. After extending the SRT from 17.2 to 68.2 d, the relative abundance of Tetrasphaera increased from 3.1% to 12.1%, and the TP removal efficiency maintained above 92%. The internal circulation results indicated that after extending the SRT, glycogen and polyhydroxybutyrate were co-synthesized during the anaerobic stage, which enhanced the driving force of nutrient removal. Analysis of the microbial composition and functional gene prediction indicated that efficient phosphorus removal can be attributed to the enrichment of Tetrasphaera at long SRT. Overall, the synergistic mechanisms of Tetrasphaera in the organic matter degradation and phosphorus removal processes were integrated into the MPSR. [ABSTRACT FROM AUTHOR]

Introduction: Pompe disease is caused by a rare biallelic mutation in the GAA gene resulting in acid α-glucosidase deficiency and glycogen accumulation. Aim: We analyzed hospital admissions associated with the administration of Myozyme®, utilizing the French hospital discharge database, known in France as the Programme de Médicalisation des Systèmes d'Information (PMSI), which comprehensively captures all hospital activity within the country. Methods: In this observational study, we examined hospitalization records from April 4, 2012, to December 31, 2019, within the PMSI database, focusing on admissions where Myozyme® was administered. We particularly investigated the incidence of critical care admissions and adverse events (AEs) related to Myozyme®. Results: From 2012 to 2019, approximately 26,714 hospital stays involving Myozyme® administration were recorded for 239 patients. Most (96.6%) of these were outpatient stays, with only 3.2% in critical care. Furthermore, hospitalizations without critical care needs increased from 96% in 2012 to 99% in 2019. Of the patients receiving at least one infusion, 997 critical care admissions were recorded, with 781 (78.3%) occurring concurrent with or the day after the Myozyme® treatment without directly correlating to adverse effects of enzyme therapy. Conclusions: The analysis of the French hospital discharge database indicated that Myozyme® was associated with a low incidence of AEs and complications in a hospital context, supporting the consideration of its safe use in home-infusion settings. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the impact of short-term fasting and subsequent re-feeding cycles on compensatory growth performance, blood glucose levels, and digestive enzyme activity in mono-sex juvenile Nile tilapia (Oreochromis niloticus) over a 60-day period. A total of 150 juvenile Nile tilapia (Avg. wt. 9.34 ± 0.97 g) were allocated into five treatment groups: a control group (continuously fed) and four fasting groups—T1 (1-day fasting), T2 (3-day fasting), T3 (5-day fasting), and T4 (7-day fasting). Re-feeding occurred for 7 days in each group immediately following the fasting period in a recurring cycle. The average weight gain, specific growth rate, and feed efficiency ratio significantly (p < 0.05) declined starting from the T3 group. Blood glucose levels during fasting significantly decreased starting from the T2 group, but after re-feeding, they returned to levels comparable to the control group. The liver glycogen levels significantly (p ≤ 0.05) decreased during fasting and completely recovered upon re-feeding, while muscle glycogen levels did not show any significant (p ≤ 0.05) changes throughout the experimental duration. The activities of the digestive enzymes amylase and lipase significantly (p ≤ 0.05) decreased during fasting starting from T1 and T2 groups, respectively, but after re-feeding, they returned to the levels seen in the control group. In contrast, the protease enzyme levels during the fasting period initially increased up to the T2 group and subsequently returned to control levels in the T4 group. The findings of this study indicate that only the groups that experienced very short fasting periods, specifically up to the T2 group, attained body weights like the control group upon re-feeding due to compensatory growth. Therefore, this study concluded that implementing up to 3 days of fasting followed by 7 days of re-feeding in multiple cycles can serve as a strategy for minimizing input costs in tilapia farming. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of adding chromium-methionine (Cr-meth) chelate in extruded diets containing reduced protein content on growth performance, carcass composition, nutrient retention, and hematobiochemical responses in Nile tilapia juveniles. The fish were fed with two control diets (no Cr-meth): positive control (311 g kg−1 of crude protein, estimated 258 g kg−1 of digestible protein) and negative control (255 g kg−1 of crude protein, estimated 207 g kg−1 of digestible protein). Another five experimental diets (mean 251 g kg−1 of crude protein, mean estimated 204 g kg−1 of digestible protein) were supplemented with 0.2, 0.4, 0.6, 0.8, and 1.0 mg Cr-meth kg diet−1. Juveniles (34.31 g) were organized in a randomized design (seven treatments in triplicate) in 21 tanks (250 L) and fed until apparent satiety. The experiment lasted 9 weeks. Fish fed 0.8 and 1.0 mg Cr-meth kg diet−1 showed zootechnical variables similar to the positive control. The reduced protein diets showed lower costs, and supplementation with 0.91 mg kg−1 of chromium matched the profitability observed in the positive control diet. Carcass gross energy and energy retention, plasma cholesterol (total and LDL), and triglycerides values were higher in fish fed 0.6 mg Cr-meth kg diet−1 than in the positive control. Treatments with dietary Cr-meth (mainly between 0.4 and 0.8 mg kg−1) decreased carcass Cr, selenium, and copper retention and increased carcass nitrogen retention and muscle glycogen levels compared to the positive control. This treatment (positive control) also had lower values for total leukocytes and monocytes, respectively, than fish fed 0.2 and 0.4 mg Cr-meth kg diet−1 and for eosinophils and lymphocytes than fish fed 0.8 mg Cr-meth kg diet−1. In conclusion, we recommend supplementation with 0.8 mg Cr-meth kg diet−1 for diets with low protein content, as it produces a dietary protein-sparing effect, reducing costs, improving immune defense, muscle glycogen, and nitrogen retention without compromising growth performance, physiology, and fish metabolism. [ABSTRACT FROM AUTHOR]

Astrocyte glycogenolysis shapes ventromedial hypothalamic nucleus (VMN) regulation of glucostasis in vivo. Glucose transporter-2 (GLUT2), a plasma membrane glucose sensor, controls hypothalamic primary astrocyte culture glycogen metabolism in vitro. In vivo gene silencing tools and single-cell laser-catapult-microdissection/multiplex qPCR techniques were used here to examine whether GLUT2 governs dorsomedial (VMNdm) and/or ventrolateral (VMNvl) VMN astrocyte metabolic sensor and glycogen metabolic enzyme gene profiles. GLUT2 gene knockdown diminished astrocyte GLUT2 mRNA in both VMN divisions. Hypoglycemia caused GLUT2 siRNA-reversible up-regulation of this gene profile in the VMNdm, but down-regulated VMNvl astrocyte GLUT2 transcription. GLUT2 augmented baseline VMNdm and VMNvl astrocyte glucokinase (GCK) gene expression, but increased (VMNdm) or reduced (VMNvl) GCK transcription during hypoglycemia. GLUT2 imposed opposite control, namely stimulation versus inhibition of VMNdm or VMNvl astrocyte 5'-AMP-activated protein kinase-alpha 1 and -alpha 2 gene expression, respectively. GLUT2 stimulated astrocyte glycogen synthase (GS) gene expression in each VMN division. GLUT2 inhibited transcription of the AMP-sensitive glycogen phosphorylase (GP) isoform GP-brain type (GPbb) in each site, yet diminished (VMNdm) or augmented (VMNvl) astrocyte GP-muscle type (GPmm) mRNA. GLUT2 enhanced VMNdm and VMNvl glycogen accumulation during euglycemia, and curbed hypoglycemia-associated VMNdm glycogen depletion. Results show that VMN astrocytes exhibit opposite, division-specific GLUT2 transcriptional responsiveness to hypoglycemia. Data document divergent GLUT2 control of GCK, AMPK catalytic subunit, and GPmm gene profiles in VMNdm versus VMNvl astrocytes. Ongoing studies seek to determine how differential GLUT2 regulation of glucose and energy sensor function and glycogenolysis in each VMN location may affect local neuron responses to hypoglycemia. [ABSTRACT FROM AUTHOR]

Although physiology ensures homeostasis and fitness in a particular environment, and ecological shifts cannot be realized without physiological changes, metabolic transformations during animal adaptive radiations still remain unexplored. We present a study of energy reserve storage in the salmonid assemblage inhabiting a cold-water Lake Kronotskoe. This assemblage diversified from Salvelinus malma and includes eight distinct ecomorphs with contrasting lifestyles and trophic specializations. We hypothesized that ecomorphs differ in energy storage and expenditure, and that their metabolic phenotypes should be among the primary targets of natural selection. To test this hypothesis, we compared the stored amount and ratio of carbohydrates, lipids, circulating peptides that supply the citric acid cycle, as well as proxy indicators of metabolic rate, the blood levels of plasma proteins (including albumin) and hemoglobin. Among ecomorphs, numerous significant differences in physiological parameters were found, closely related to the composition of food, the depth of habitat, and determined by internal factors, probably genetics. Each ecomorph has a specific metabolic phenotype corresponding to its tropho-ecological specialization and lifestyle. Metabolically advanced predators accumulate lipids; littoral insectivorous morphs grow slower and accumulate glycogen; amphipod feeders do not accumulate spare substances; the deepwater consumer of silt benthos differs in the most divergent physiological characteristics. We assume a specific selection on endocrine regulators of energy metabolism during the adaptive radiation of the assemblage, among which the most plausible candidates are thyroid hormones and leptin. [ABSTRACT FROM AUTHOR]

Glycogen storage, conversion and utilization in astrocytes play an important role in brain energy metabolism. The conversion of glycogen to lactate through glycolysis occurs through the coordinated activities of various enzymes and inhibition of this process can impair different brain processes including formation of long-lasting memories. To replenish depleted glycogen stores, astrocytes undergo glycogen synthesis, a cellular process that has been shown to require transcription and translation during specific stimulation paradigms. However, the detail nuclear signaling mechanisms and transcriptional regulation during glycogen synthesis in astrocytes remains to be explored. In this report, we study the molecular mechanisms of vasoactive intestinal peptide (VIP)-induced glycogen synthesis in astrocytes. VIP is a potent neuropeptide that triggers glycogenolysis followed by glycogen synthesis in astrocytes. We show evidence that VIP-induced glycogen synthesis requires CREB-mediated transcription that is calcium dependent and requires conventional Protein Kinase C but not Protein Kinase A. In parallel to CREB activation, we demonstrate that VIP also triggers nuclear accumulation of the CREB coactivator CRTC2 in astrocytic nuclei. Transcriptome profiles of VIP-induced astrocytes identified robust CREB transcription, including a subset of genes linked to glucose and glycogen metabolism. Finally, we demonstrate that VIP-induced glycogen synthesis shares similar as well as distinct molecular signatures with glucose-induced glycogen synthesis, including the requirement of CREB-mediated transcription. Overall, our data demonstrates the importance of CREB-mediated transcription in astrocytes during stimulus-driven glycogenesis. [ABSTRACT FROM AUTHOR]

Ferulic acid is a naturally occurring polyphenolic compound that is generally found in plants, vegetables, and fruits. Although ferulic acid has been widely utilized to treat a variety of illnesses, there have been no studies done yet on its potential protective effects on the glycoprotein moiety in streptozotocin-induced diabetic rats. The goal of this study was to concentrate on this issue. Streptozotocin was administered intraperitoneally once to male Wistar albino rats to cause diabetes. Using commercial diagnostic kits, we assessed plasma glucose and glycated haemoglobin (HbA1c). Plasma insulin level was assayed with the help of an enzyme—linked immunosorbent assay (ELISA) kit and other assays were made biochemically. In diabetic rats, the levels of blood glucose and HbA1c were noticeably elevated whereas the levels of plasma insulin and haemoglobin (Hb) were significantly lowered. Additionally, the levels of carbohydrate metabolic enzymes such as hexokinase, glucose-6-phosphate dehydrogenase were significantly reduced, while fructose-1, 6-bisphosphatase and glucose-6-phosphatase levels were significantly increased. The glycogen metabolic enzymes- glycogen synthase level was significantly decreased whereas glycogen reductase level was increased with a concomitant decrease in glycogen content. Additionally, diabetic rats had dramatically different levels of glycoprotein moiety substances such hexose, hexosamine, fucose, and sialic acid. Ferulic acid and glibenclamide administration reversed all the altered biochemical profiles by correcting the hyperglycemia via enhanced insulin secretion and regulation of carbohydrate metabolism. In terms of its impact on different parameters, ferulic acid had an effect similar to that of glibenclamide. Hence, ferulic acid can be used as an antidiabetic drug. [ABSTRACT FROM AUTHOR]

Under nitrogen deprivation (-N), cyanobacterium Synechocystis sp. PCC 6803 exhibits growth arrest, reduced protein content, and remarkably increased glycogen accumulation. However, producing glycogen under this condition requires a two-step process with cell transfer from normal to -N medium. Metabolic engineering and chemical treatment for rapid glycogen accumulation can bypass the need for two-step cultivation. For example, recent studies indicate that individually disrupting hydrogen (H2) or poly(3-hydroxybutyrate) (PHB) synthesis, or treatment with methyl viologen (MV), effectively increases glycogen accumulation in Synechocystis. Here we explore the effects of disrupted H2 or poly(3-hydroxybutyrate) synthesis, together with MV treatment to on enhanced glycogen accumulation in Synechocystis grown in normal medium. Wild-type cells without MV treatment exhibited low glycogen content of less than 6% w/w dry weight (DW). Compared with wild type, disrupting PHB synthesis combined with MV treatment did not increase glycogen content. Disrupted H₂ production without MV treatment yielded up to 11% w/w DW glycogen content. Interestingly, when combined, disrupted H2 production with MV treatment synergistically enhanced glycogen accumulation to 51% and 59% w/w DW within 3 and 7 days, respectively. Metabolomic analysis suggests that MV treatment mediated the conversion of proteins into glycogen. Metabolomic and transcriptional-expression analysis suggests that disrupted H2 synthesis under MV treatment positively influenced glycogen synthesis. Disrupted H₂ synthesis under MV treatment significantly increased NADPH levels. This increased NADPH content potentially contributed to the observed enhancements in antioxidant activity against MV-induced oxidants, O2 evolution, and metabolite substrates levels for glycogen synthesis in normal medium, ultimately leading to enhanced glycogen accumulation in Synechocystis. Key message: Combining disrupted hydrogen-gas synthesis and the treatment by photosynthesis electron-transport inhibitor significantly enhance glycogen production in cyanobacteria. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of a 4-week live high train low (LHTL; FiO2 ~ 13.5%), intervention, followed by a tapering phase, on muscle glycogen concentration. Fourteen physically active males (28 ± 6 years, 81.6 ± 15.4 kg, 179 ± 5.2 cm) were divided into a control group (CON; n = 5), and the group that performed the LHTL, which was exposed to hypoxia (LHTL; n = 9). The subjects trained using a one-legged knee extension exercise, which enabled four experimental conditions: leg training in hypoxia (TLHYP); leg control in hypoxia (CLHYP, n = 9); leg trained in normoxia (TLNOR, n = 5), and leg control in normoxia (CLNOR, n = 5). All participants performed 18 training sessions lasting between 20 and 45 min [80–200% of intensity corresponding to the time to exhaustion (TTE) reached in the graded exercise test]. Additionally, participants spent approximately 10 h day−1 in either a normobaric hypoxic environment (14.5% FiO2; ~ 3000 m) or a control condition (i.e., staying in similar tents on ~ 530 m). Thereafter, participants underwent a taper protocol consisting of six additional training sessions with a reduced training load. SpO2 was lower, and the hypoxic dose was higher in LHTL compared to CON (p < 0.001). After 4 weeks, glycogen had increased significantly only in the TLNOR and TLHYP groups and remained elevated after the taper (p < 0.016). Time to exhaustion in the LHTL increased after both the 4-week training period and the taper compared to the baseline (p < 0.001). Although the 4-week training promoted substantial increases in muscle glycogen content, TTE increased in LHTL condition. [ABSTRACT FROM AUTHOR]

The objectives of this study were to investigate the anti-fatigue effects of Paris polyphylla polysaccharide component 1 (PPPm-1) and explore its mechanisms. A mouse model of exercise-induced fatigue was established by weight-bearing swimming to observe the effects of different concentrations of PPPm-1 on weight-bearing swimming time. The anti-fatigue effect of PPPm-1 was determined by the effects of contraction amplitude, contraction rate, and diastolic rate of the frog gastrocnemius muscle in vivo before and after infiltration with 5 mg/mL PPPm-1. The effects of PPPm-1 on the contents of blood lactate, serum urea nitrogen, hepatic glycogen, muscle glycogen in the exercise fatigue model of mice, and acetylcholine (ACh) content and acetylcholinesterase (AChE) activity at the junction of the frog sciatic nerve-gastrocnemius under normal physiological, and Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities of the frog gastrocnemius were determined by enzyme-linked immunosorbent assay (ELISA), to investigate the anti-fatigue mechanisms of PPPm-1. The results showed that PPPm-1 could significantly prolong the weight-bearing swimming time in mice (P < 0.01), decrease the contents of blood lactate and serum urea nitrogen, increase the contents of the hepatic glycogen and muscle glycogen of mice after exercise fatigue compared with those of the control group, and there was extremely significant difference in most indicators (P < 0.01). The 5 mg/mL of PPPm-1 could significantly promote the contraction amplitude, contraction rate, and relaxation rate of the gastrocnemius muscle in the frogs, and the content of ACh at the junction of the frog sciatic nerve-gastrocnemius (P < 0.01), but it had obvious inhibitory effetc on the activity of AChE at the junction of the frog sciatic nerve-gastrocnemius (P < 0.01). PPPm-1 could increase the Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities of gastrocnemius in the frogs (for Ca2+-Mg2+-ATPase, P < 0.01). The above results suggested that the PPPm-1 had a good anti-fatigue effect, and its main mechanisms were related to improving endurance and glycogen reserve, reducing glycogen consumption, lactate and serum urea nitrogen accumulation, and promoting Ca2+ influx. [ABSTRACT FROM AUTHOR]

Background: Daily nutrition plays an important role in supporting training adaptions and endurance performance. The objective of this 10-week study was to investigate the consequences of varying carbohydrate consumption and the glycaemic index (GI) together with an endurance training regimen on substrate oxidation, muscle energy storage and endurance performance under free-living conditions. Sixty-five moderately trained healthy men (29 ± 4 years; VO2 peak 55 ± 8 mL min−1 kg−1) were randomized to one of three different nutritional regimes (LOW-GI: 50–60% CHO with ≥ 65% of these CHO with GI < 50 per day, n = 24; HIGH-GI: 50–60% CHO with ≥ 65% CHO with GI > 70 per day, n = 20; LCHF: ≤ 50 g CHO daily, n = 21). Metabolic alterations and performance were assessed at baseline (T0) and after 10 weeks (T10) during a graded exercise treadmill test. Additionally, a 5 km time trial on a 400-m outdoor track was performed and muscle glycogen was measured by magnet resonance spectroscopy. Results: Total fat oxidation expressed as area under the curve (AUC) during the graded exercise test increased in LCHF (1.3 ± 2.4 g min−1 × km h−1, p < 0.001), remained unchanged in LOW-GI (p > 0.05) and decreased in HIGH-GI (− 1.7 ± 1.5 g min−1 × km h−1, p < 0.001). After the intervention, LOW-GI (− 0.4 ± 0.5 mmol L−1 × km h−1, p < 0.001) and LCHF (− 0.8 ± 0.7 mmol L−1 × km h−1, p < 0.001) showed significantly lower AUC of blood lactate concentrations. Peak running speed increased in LOW-GI (T0: 4.3 ± 0.4 vs. T10: 4.5 ± 0.3 m s−1, p < 0.001) and HIGH-GI (T0: 4.4 ± 0.5 vs. T10: 4.6 ± 0.4 m s−1), while no improvement was observed in LCHF. Yet, time trial performance improved significantly in all groups. Muscle glycogen content increased for participants in HIGH-GI (T0: 97.3 ± 18.5 vs. T10: 144.5 ± 39.8 mmol L wet-tissue−1, p = 0.027) and remained unchanged in the LOW-GI and the LCHF group. At the last examination, muscle glycogen concentration was significantly higher in LOW-GI compared to LCHF (p = 0.014). Conclusion: Changes in fat oxidation were only present in LCHF, however, lower lactate concentrations in LOW-GI resulted in changes indicating an improved substrate metabolism. Compared to a LCHF diet, changes in peak running speed, and muscle glycogen stores were superior in LOW- and HIGH-GI diets. The low GI diet seems to have an influence on substrate metabolism without compromising performance at higher intensities, suggesting that a high-carbohydrate diet with a low GI is a viable alternative to a LCHF or a high GI diet. Trial registration: Clinical Trials, NCT05241730. https://clinicaltrials.gov/study/NCT05241730. Registered 25 January 2021. Key Points: While only the LCHF diet showed an improvement in fat oxidation and the HIGH-GI group increased peak running speed and showed a trend towards an improvement in time to exhaustion, the LOW-GI group appears to combine both effects on substrate metabolism and performance. Administered under free-living conditions, energy intake changed in LOW-GI diet, possible due to higher intake of fibre, stable insulin levels and associated higher feeling of satiety. Energy intake in HIGH-GI showed no changes and in LCHF a trend towards a reduced intake was observed. While changes in body weight and composition were more pronounced in LOW-GI and LCHF group, muscle energy storage showed beneficial improvements in endurance runners on a high glycaemic index diet. With the muscle glycogen content being significantly lower in LCHF compared to LOW-GI group, it can be assumed that this might be a limiting factor in maximum values for the graded exercise test. [ABSTRACT FROM AUTHOR]

Demonstration of glycogen in tissue holds considerable diagnostic relevance across various pathological conditions, particularly in certain tumors. The histochemical staining of glycogen using methods utilizing Schiff's reagents is subject to influences arising from the type of fixative, fixation temperature, and oxidizing agents employed. This study aimed to assess diverse fixatives, fixation temperatures, and oxidizing agents, each with variable treatment durations, in conjunction with Schiff's reagent for optimal glycogen demonstration. Paraffin blocks derived from a rabbit's liver served as the experimental substrate, encompassing 340 paraffin sections subjected to different procedures. For tissues fixed at 4 °C, good staining outcomes, as determined by the periodic acid–Schiff (PAS) stain, were observed with 10% neutral buffered formalin (NBF), 80% alcohol, and Bouin's solution. Tissues fixed at room temperature (RT) demonstrated good PAS staining results with both 10% NBF and 80% alcohol. Notably, other oxidizing agents exhibited poor outcomes across all fixatives and fixation temperature, with two exceptions, as satisfactory staining results were obtained when using 5% chromic acid. Consequently, Both 10% NBF and 80% emerge as preferred fixatives of choice for glycogen demonstration when coupled with PAS stain. It is noteworthy that Bouin's solution could also provide good outcomes when fixation occurred at 4 °C. [ABSTRACT FROM AUTHOR]

The study of phosphorylase kinase (PhK)-regulated glycogen metabolism has contributed to the fundamental understanding of protein phosphorylation; however, the molecular mechanism of PhK remains poorly understood. Here we present the high-resolution cryo-electron microscopy structures of human muscle PhK. The 1.3-megadalton PhK α4β4γ4δ4 hexadecamer consists of a tetramer of tetramer, wherein four αβγδ modules are connected by the central β4 scaffold. The α- and β-subunits possess glucoamylase-like domains, but exhibit no detectable enzyme activities. The α-subunit serves as a bridge between the β-subunit and the γδ subcomplex, and facilitates the γ-subunit to adopt an autoinhibited state. Ca2+-free calmodulin (δ-subunit) binds to the γ-subunit in a compact conformation. Upon binding of Ca2+, a conformational change occurs, allowing for the de-inhibition of the γ-subunit through a spring-loaded mechanism. We also reveal an ADP-binding pocket in the β-subunit, which plays a role in allosterically enhancing PhK activity. These results provide molecular insights of this important kinase complex. High-resolution cryo-EM study of human muscle phosphorylase kinase reveals its complex structure and how calcium ions activate it, offering insights into glycogen metabolism and kinase regulation. [ABSTRACT FROM AUTHOR]

Assessing habitat quality is a major goal of conservationists and restoration practitioners, but to associate habitat quality with biomarkers of vagile animals, the biomarkers must respond rapidly. Here, we identified a biomarker capable of rapidly detecting food limitation in the imperiled Delta Smelt (Hypomesus transpacificus), a pelagic fish endemic to the San Francisco Estuary (SFE). We conducted an experiment with fed and unfed treatments of hatchery-raised, sub-adult Delta Smelt that were sampled at 12 time points: 0, 1, 2, 3, 4, 5, 6, 7, 9, 11, 14, and 21 days. We then compared four biomarkers using Day 21 fish: RNA/DNA in liver, triglycerides in liver, glycogen in liver, and glycogen in muscle. Of the liver endpoints, glycogen had the largest difference between treatments at Day 21, so we compared it to muscle glycogen across all time points. Liver glycogen declined by 60% after 1 day of fasting and remained depressed in the fasting treatment across all subsequent time points. Muscle glycogen also responded rapidly, taking only 2 days to decline by 39% in the fasting treatment, but the difference was inconsistent across subsequent time points. When applied to hatchery-released Delta Smelt collected from the SFE, liver glycogen concentrations were less than half that of the fed hatchery fish, consistent with the hypothesis of food limitation in the wild, but also several other potential causes. This study highlights the utility of liver glycogen as an indicator of recent foraging success in Delta Smelt. [ABSTRACT FROM AUTHOR]

Glycogen serves as a metabolic sink in cyanobacteria. Glycogen deficiency causes the extracellular release of distinctive metabolites such as pyruvate and 2-oxoglutarate upon nitrogen depletion; however, the mechanism has not been fully elucidated. This study aimed to elucidate the mechanism of carbon partitioning in glycogen-deficient cyanobacteria. Extracellular and intracellular metabolites in a glycogen-deficient ΔglgC mutant of Synechococcus elongatus PCC 7942 were comprehensively analyzed. In the presence of a nitrogen source, the ΔglgC mutant released extracellular glutamate rather than pyruvate and 2-oxoglutarate, whereas its intracellular glutamate level was lower than that in the wild-type strain. The de novo synthesis of glutamate increased in the ΔglgC mutant, suggesting that glycogen deficiency enhanced carbon partitioning into glutamate and extracellular excretion through an unidentified transport system. This study proposes a model in which glutamate serves as the prime extracellular metabolic sink alternative to glycogen when nitrogen is available. This study revealed that a glycogen-deficient mutant cyanobacteria highly released glutamate extracellularly when nitrogen is available, proposing a model in which glutamate serves as the prime extracellular metabolic sink alternative to glycogen. [ABSTRACT FROM AUTHOR]

Tryptophan (Trp) is a nutritionally essential amino acid for fish because it cannot be synthesized in the body. This study aimed to estimate the digestible Trp requirement in diets for tambaqui (Colossoma macropomum) in the fattening phase (120.44 ± 0.34 g). Diets containing different digestible Trp concentrations (2.16, 2.73, 3.30, 3.86, 4.43, and 5.00 g kg–1) were analyzed for 60 days. After, zootechnical performance, whole-body deposition, and hematobiochemical parameters were analyzed. According to quadratic regression, the best growth performance and whole-body deposition results were found in fish fed with diets between 3.30 and 3.86 g Trp kg–1 (p < 0.05). The quadratic regression showed that the dietary Trp requirement estimated based on weight gain, specific growth rate, thermal growth coefficient, and the feed conversion ratio was 3.66, 3.63, 3.67, and 3.42 g Trp kg diet–1, respectively (p < 0.05). According to quadratic regression, body protein deposition, body fat deposition, body ash deposition, and nitrogen retention efficiency, the best values of dietary Trp were between 3.58 and 3.73 g kg–1 (p < 0.05). The quadratic regression showed a reduction of liver AST activity in treatments between 2.73 and 3.86 g Trp kg diet–1, and for liver glycogen levels, the highest values were found in fish fed 5.00 g Trp kg diet–1 (p < 0.05). Plasmatic and hematological variables were not influenced by different Trp levels in the diet (p > 0.05). Tambaqui presented the best growth performance and whole-body deposition without affecting the hematological and plasma status and reducing liver parameters (AST and glycogen) when fed between 3.42 and 3.73 g Trp kg diet–1 (1.18–1.29% dietary protein). [ABSTRACT FROM AUTHOR]

Background: Physique athletes are ranked by a panel of judges against the judging criteria of the corresponding division. To enhance on-stage presentation and performance, competitors in certain categories (i.e. bodybuilding and classic physique) achieve extreme muscle size and definition aided by implementing acute "peaking protocols" in the days before competition. Such practices can involve manipulating nutrition and training variables to increase intramuscular glycogen and water while minimising the thickness of the subcutaneous layer. Carbohydrate manipulation is a prevalent strategy utilised to plausibly induce muscle glycogen supercompensation and subsequently increase muscle size. The relationship between carbohydrate intake and muscle glycogen saturation was first examined in endurance event performance and similar strategies have been adopted by physique athletes despite the distinct physiological dissimilarities and aims between the sports. Objectives: The aim of this narrative review is to (1) critically examine and appraise the existing scientific literature relating to carbohydrate manipulation practices in physique athletes prior to competition; (2) identify research gaps and provide direction for future studies; and (3) provide broad practical applications based on the findings and physiological reasoning for coaches and competitors. Findings: The findings of this review indicate that carbohydrate manipulation practices are prevalent amongst physique athletes despite a paucity of experimental evidence demonstrating the efficacy of such strategies on physique performance. Competitors have also been observed to manipulate water and electrolytes in conjunction with carbohydrate predicated on speculative physiological mechanisms which may be detrimental for performance. Conclusions: Further experimental evidence which closely replicates the nutritional and training practices of physique athletes during peak week is required to make conclusions on the efficacy of carbohydrate manipulation strategies. Quasi-experimental designs may be a feasible alternative to randomised controlled trials to examine such strategies due to the difficulty in recruiting the population of interest. Finally, we recommend that coaches and competitors manipulate as few variables as possible, and experiment with different magnitudes of carbohydrate loads in advance of competition if implementing a peaking strategy. Key Points: Physique athletes regularly implement "peak week" strategies based on the endurance training research. At present it appears that carbohydrate (CHO) loading strategies may increase muscle size; however, the effects on overall aesthetic performance are unknown. Due to a lack of data, it is difficult to make detailed peak week recommendations. Rather, it may be advisable to load with 3–12 g/kg/BM of CHO to increase muscle glycogen content, with this broad range representing different individual and divisional requirements. To optimise the magnitude of CHO load, coaches and competitors could establish an individual response pattern before competition by practicing and trialling peaking strategies in similar physiological conditions to peak week, and by using information from previous competitions. Further, manipulating as few variables at a time as possible could have the greatest physiological and psychological benefits. Experimental designs which assess visual physique changes while placing participants in ecologically valid physiological conditions are needed to fully elucidate the effects of CHO, water, and electrolyte manipulation peaking strategies. [ABSTRACT FROM AUTHOR]

In soccer, players must perform a variety of sport-specific skills usually during or immediately after running, often at sprint speed. The quality of the skill performed is likely influenced by the volume of work done in attacking and defending over the duration of the match. Even the most highly skilful players succumb to the impact of fatigue both physical and mental, which may result in underperforming skills at key moments in a match. Fitness is the platform on which skill is performed during team sport. With the onset of fatigue, tired players find it ever more difficult to successfully perform basic skills. Therefore, it is not surprising that teams spend a large proportion of their training time on fitness. While acknowledging the central role of fitness in team sport, the importance of team tactics, underpinned by spatial awareness, must not be neglected. It is well established that a high-carbohydrate diet before a match and, as a supplement during match play, helps delay the onset of fatigue. There is some evidence that players ingesting carbohydrate can maintain sport-relevant skills for the duration of exercise more successfully compared with when ingesting placebo or water. However, most of the assessments of sport-specific skills have been performed in a controlled, non-contested environment. Although these methods may be judged as not ecologically valid, they do rule out the confounding influences of competition on skill performance. The aim of this brief review is to explore whether carbohydrate ingestion, while delaying fatigue during match play, may also help retain sport soccer-specific skill performance. [ABSTRACT FROM AUTHOR]

Tambaqui (Colossoma macropomum) is a species of great cultural and economic importance in aquaculture in the Amazon region. Methionine is considered the first limiting sulfur amino acid in practical fish diets, which encourages investigating its use in diets for tambaqui. This study aimed to verify the digestible methionine plus cystine (Met + Cys) requirement in diets for tambaqui (89.52 ± 0.53 g) for 60 days. The treatments investigated were: 6.50, 7.80, 9.10, 10.40, 11.70, and 13.00 g Met + Cys kg diet–1. The estimated requirement based on final weight, weight gain, feed conversion ratio, and specific growth rate was 9.04, 8.92, 8.91, and 8.58 g Met + Cys kg diet–1, respectively, while on body protein deposition, body fat deposition, body ash deposition, and nitrogen retention efficiency was 9.29, 9.20, 9.19, and 8.72 g Met + Cys kg diet–1, respectively. Linear regression demonstrated that increased digestible Met + Cys in the diet decreased plasma total protein, globulin, and liver total protein levels. Quadratic regression showed that the highest value for liver glycogen was found with a 10.40 g Met + Cys kg diet–1. Another quadratic regression demonstrated a lower hepatic aspartate aminotransferase (AST) enzymatic activity in fish fed between 7.80 and 11.70 g Met + Cys kg diet–1. The different treatments did not influence the erythrogram. In conclusion, when considering an integrative view of the results for growth performance, whole-body deposition, and liver parameters without harming the physiological and metabolic status, we recommended choosing a diet with digestible Met + Cys between 8.58 and 9.29 g kg− 1 for tambaqui. [ABSTRACT FROM AUTHOR]

The effect of stevia leaf extract, saccharinate, and cyclamate in various dosages on the glycogen content of blood leukocytes in C57BL/6 mice as a necessary substrate for the realization of phagocytosis was studied. An increase in glycogen content was found in all experimental groups treated with sweeteners at a dosage of 10 mg/g of body weight. The effect of sweeteners on the differential leukocyte counts was found only in mice receiving the stevia leaf extract at a dosage of 10 mg/g of body weight manifested as an increase neutrophil-to-lymphocyte ratio (NLR). The data obtained expand our understanding of the metabolism of sugar substitutes in an organism and their influence on physiological systems, in particular, the hematopoietic and immune systems. [ABSTRACT FROM AUTHOR]

This article discusses current concepts of the role of sleep in cellular energy metabolism, the processes of neuroplasticity, and cleansing of the cerebral parenchyma from metabolic products. Numerous studies have demonstrated that prolonged waking poses a challenge to the brain, both energetically and physiologically. This article outlines the kinetics of the biochemical processes responsible for replenishing energy reserves during sleep. The roles of ATP, adenosine, and glycogen in these processes are noted. Depletion of the substrates of cellular energy metabolism leads to stress on the endoplasmic reticulum and protein-unfolding reactions. These changes are paralleled by increases in synaptic conductivity, which aggravates energy disorders because increases in the size and number of synapses imply increases in energy costs. The level of glymphatic clearance during waking is significantly lower than that during sleep, and metabolic products cannot be eliminated at the necessary rate. [ABSTRACT FROM AUTHOR]

Metabolic stress caused by excess nutrients accelerates aging. We recently demonstrated that the newly discovered enzyme glycerol-3-phosphate phosphatase (G3PP; gene Pgp), which operates an evolutionarily conserved glycerol shunt that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol, counters metabolic stress and promotes healthy aging in C. elegans. However, the mechanism whereby G3PP activation extends healthspan and lifespan, particularly under glucotoxicity, remained unknown. Here, we show that the overexpression of the C. elegans G3PP homolog, PGPH-2, decreases fat levels and mimics, in part, the beneficial effects of calorie restriction, particularly in glucotoxicity conditions, without reducing food intake. PGPH-2 overexpression depletes glycogen stores activating AMP-activate protein kinase, which leads to the HLH-30 nuclear translocation and activation of autophagy, promoting healthy aging. Transcriptomics reveal an HLH-30-dependent longevity and catabolic gene expression signature with PGPH-2 overexpression. Thus, G3PP overexpression activates three key longevity factors, AMPK, the TFEB homolog HLH-30, and autophagy, and may be an attractive target for age-related metabolic disorders linked to excess nutrients. Activation of the glycerol shunt mimics calorie restriction, protects from glucotoxicity, and promotes healthy aging. Here, Possik et al. uncover the underlying mechanism and identify the AMPK-TFEB autophagy pathway as critical to the healthy aging phenotype. [ABSTRACT FROM AUTHOR]

Histological and cytological changes in the liver and small intestine tissues of Spermophilus citellus (S. citellus) during and post-hibernation were examined. Microphotographs were taken under the light and electron microscope for this purpose. During hibernation, it was determined that the number of Kupffer cells in the liver increased, and the areas of PAS-negative staining increased. In the small intestine, it was determined that the length of the villi was shortened and the surface area was reduced, and there was a decrease in the crypt depth. In post-hibernation, a decrease in the number of Kupffer cells and an increase in PAS-positive areas were observed in the liver. In post-hibernation, in the small intestine, an increase in villus lengths, villus surface area, and crypt depth was determined. An independent samples t-test was performed to analyze the data obtained about the small intestine. The results will reference studies on the liver and digestive tract. [ABSTRACT FROM AUTHOR]

Demonstration of glycogen can be done in different lesions and is considered diagnostically significant, mainly in some tumors. Glycogen staining is affected by the type of fixative, the temperature of fixation, and the staining technique. Grocott's methenamine (hexamine) silver technique quality was assessed after four different types of fixatives at two different temperatures [Bouin's solution, 10% neutral buffered formalin (NBF), 80% alcohol, and Rossman's solution at room temperature (RT) and 4 °C, for 24 h]. These variables were studied to optimize this technique for glycogen demonstration. Archived paraffin blocks were used in this study. They were prepared from one rabbit's liver, and 32 paraffin sections were prepared and stained with Grocott's methenamine (hexamine) silver technique. Eighty percent alcohol provided the highest staining quality scores at both RT and 4 °C in comparison with the other fixatives. We concluded that 80% alcohol at 4 °C seems to be the fixative of choice for glycogen with the Grocott's methenamine (hexamine) silver technique at the level of this study. [ABSTRACT FROM AUTHOR]

Muscle glycogen state and carbohydrate (CHO) supplementation before and during exercise may impact responses to high-intensity interval training (HIIT). This study determined cardiorespiratory, substrate metabolism, muscle oxygenation, and performance when completing HIIT with or without CHO supplementation in a muscle glycogen depleted state. On two occasions, in a cross-over design, eight male cyclists performed a glycogen depletion protocol prior to HIIT during which either a 6% CHO drink (60 g.hr−1) or placebo (%CHO, PLA) was consumed. HIIT consisted of 5 × 2 min at 80% peak power output (PPO), 3 × 10-min bouts of steady-state (SS) cycling (50, 55, 60% PPO), and a time-to-exhaustion (TTE) test. There was no difference in SS V ˙ O 2 , HR, substrate oxidation and gross efficiency (GE %) between CHO and PLA conditions. A faster rate of muscle reoxygenation (%. s−1) existed in PLA after the 1st (Δ − 0.23 ± 0.22, d = 0.58, P < 0.05) and 3rd HIIT intervals (Δ − 0.34 ± 0.25, d = 1.02, P < 0.05). TTE was greater in CHO (7.1 ± 5.4 min) than PLA (2.5 ± 2.3 min, d = 0.98, P < 0.05). CHO consumption before and during exercise under reduced muscle glycogen conditions did not suppress fat oxidation, suggesting a strong regulatory role of muscle glycogen on substrate metabolism. However, CHO ingestion provided a performance benefit under intense exercise conditions commenced with reduced muscle glycogen. More research is needed to understand the significance of altered muscle oxygenation patterns during exercise. [ABSTRACT FROM AUTHOR]

The structure and properties of phytoglycogen and glycogen subjected to acid hydrolysis was investigated using amylopectin as a reference. The degradation took place in two stages and the degree of hydrolysis was in the following order: amylopectin > phytoglycogen > glycogen. Upon acid hydrolysis, the molar mass distribution of phytoglycogen or glycogen gradually shifted to the smaller and broadening distribution region, whereas the distribution of amyopectin changed from bimodal to monomodal shape. The kinetic rate constant for depolymerization of phytoglycogen, amylopectin, and glycogen were 3.45 × 10−5/s, 6.13 × 10−5/s, and 0.96 × 10−5/s, respectively. The acid-treated sample had the smaller particle radius, lower percentage of α-1,6 linkage as well as higher rapidly digestible starch fractions. The depolymerization models were built to interpret the structural differences of glucose polymer during acid treatment, which would provide guideline to improve the structure understanding and precise application of branched glucan with desired properties. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is the second leading cause of cancer-related mortality among women. Beyond the established tumourigenic role of genetic mutations, metabolic reprogramming is another key cancer hallmark. Glucose metabolism in particular is known to be prominently altered in tumours, in order to support biomass accumulation and cancer cell survival. The tumor suppressor microRNA (miRNA) miR-22 has been previously associated with a plethora of BC phenotypes such as growth, invasion-metastasis, and regulation of metabolic phenotypes such as lipid and folate metabolism. In this study, we aimed to investigate the role of miR-22 in the regulation of glucose metabolism in BC cells. Methods and results: Here we examined how miR-22 affects glucose metabolism in the MCF-7 BC cells. We found that over-expression of miR-22 caused a reduced glycolytic rate in these cells. Moreover, the miRNA also rendered MCF-7 cells more sensitive to lower glucose levels. We next unbiasedly screened the transcript levels of 84 genes relevant to glucose metabolism using the Human Glucose RT2 Profiler PCR Array. Interestingly, the strongest effect identified by this screen was the upregulation of genes involved in glycogen synthesis and the repression of gene involved in glycogen catabolism. Examination of publicly available transcriptomic datasets confirmed the correlations between expression of miR-22 and these glycogen metabolism genes in BC cells. Conclusion: This study has generated evidence for a regulatory role of miR-22 in glucose and glycogen metabolism, expanding the involvement of this miRNA in BC metabolic reprogramming. [ABSTRACT FROM AUTHOR]

The dimensional and physiological-biochemical parameters of erythrocytes, as well as the gill and heart indices, were studied in five species of marine benthic fish. The black scorpionfish Scorpaena porcus Linnaeus, 1758 and the shore rockling Gaidropsarus mediterraneus Linnaeus, 1758 differed from the other species in a larger mass of the heart and gill apparatus, which indicates more efficient transport capabilities of the circulatory system of these fish. The linear size characteristics of erythrocytes of a cartilaginous fish, the thornback ray Raja clavata Linnaeus, 1758, were 1.5–2 times higher than those of erythrocytes of S. porcus, which were the largest among the studied teleosts. The sizes of the erythrocytes of three other teleost species differed insignificantly. The amount of hemoglobin per unit surface area of erythrocyte, which reflects the efficiency of hemoglobin saturation with oxygen, insignificantly varied (0.05 to 0.071 pg/mm2) among the studied bony fish. In contrast, in the thornback ray this parameter was 2.7–3.8 times lower. The intracellular glycogen concentration, which characterizes the degree to which the erythrocyte is independent of glycemic fluctuations, was highest in cells of S. porcus (305.2 ± 35.1 mg %), while it was lowest in erythrocytes of the thornback ray R. clavata (142.8 ± 15.1 mg %). The ecto-ATPase activity was higher in large erythrocytes of S. porcus, R. clavata, and Uranoscopus scaber (4.8, 3.1, and 1.6 μmol Pin/min/mL of erythrocytes, respectively) than in smaller erythrocytes of Crenilabrus tinca and Gaidropsarus mediterraneus (0.5 and 0.4, μmol Pin/min/mL of erythrocytes, respectively). This confirms the assumption that erythrocytes use the thermal energy from hydrolysis of extracellular ATP to "warm" their own membrane, which leads to the change in the rheological characteristics of blood in the capillary blood flow. [ABSTRACT FROM AUTHOR]

Abstract Glycogen dysregulation is a hallmark of aging, and aberrant glycogen drives metabolic reprogramming and pathogenesis in multiple diseases. However, glycogen heterogeneity in healthy and diseased tissues remains largely unknown. Herein, we describe a method to define spatial glycogen architecture in mouse and human tissues using matrix‐assisted laser desorption/ionization mass spectrometry imaging. This assay provides robust and sensitive spatial glycogen quantification and architecture characterization in the brain, liver, kidney, testis, lung, bladder, and even the bone. Armed with this tool, we interrogated glycogen spatial distribution and architecture in different types of human cancers. We demonstrate that glycogen stores and architecture are heterogeneous among diseases. Additionally, we observe unique hyperphosphorylated glycogen accumulation in Ewing sarcoma, a pediatric bone cancer. Using preclinical models, we correct glycogen hyperphosphorylation in Ewing sarcoma through genetic and pharmacological interventions that ablate in vivo tumor growth, demonstrating the clinical therapeutic potential of targeting glycogen in Ewing sarcoma.

Nutrient availability in eggs can affect early metabolic orientation in birds. In chickens divergently selected on the Pectoralis major ultimate pH, a proxy for muscle glycogen stores, characterization of the yolk and amniotic fluid revealed a different nutritional environment. The present study aimed to assess indicators of embryo metabolism in pHu lines (pHu+ and pHu−) using allantoic fluids (compartment storing nitrogenous waste products and metabolites), collected at days 10, 14 and 17 of embryogenesis and characterized by 1H-NMR spectroscopy. Analysis of metabolic profiles revealed a significant stage effect, with an enrichment in metabolites at the end of incubation, and an increase in interindividual variability during development. OPLS-DA analysis discriminated the two lines. The allantoic fluid of pHu− was richer in carbohydrates, intermediates of purine metabolism and derivatives of tryptophan-histidine metabolism, while formate, branched-chain amino acids, Krebs cycle intermediates and metabolites from different catabolic pathways were more abundant in pHu+. In conclusion, the characterization of the main nutrient sources for embryos and now allantoic fluids provided an overview of the in ovo nutritional environment of pHu lines. Moreover, this study revealed the establishment, as early as day 10 of embryo development, of specific metabolic signatures in the allantoic fluid of pHu+ and pHu− lines. [ABSTRACT FROM AUTHOR]

Severe sleep deprivation (SD) has been highly associated with systemic energy wasting, such as lipid loss and glycogen depletion. Despite immune dysregulation and neurotoxicity observed in SD animals, whether and how the gut-secreted hormones participate in SD-induced disruption of energy homeostasis remains largely unknown. Using Drosophila as a conserved model organism, we characterize that production of intestinal Allatostatin A (AstA), a major gut-peptide hormone, is robustly increased in adult flies bearing severe SD. Interestingly, the removal of AstA production in the gut using specific drivers significantly improves lipid loss and glycogen depletion in SD flies without affecting sleep homeostasis. We reveal the molecular mechanisms whereby gut AstA promotes the release of an adipokinetic hormone (Akh), an insulin counter-regulatory hormone functionally equivalent to mammalian glucagon, to mobilize systemic energy reserves by remotely targeting its receptor AstA-R2 in Akh-producing cells. Similar regulation of glucagon secretion and energy wasting by AstA/galanin is also observed in SD mice. Further, integrating single-cell RNA sequencing and genetic validation, we uncover that severe SD results in ROS accumulation in the gut to augment AstA production via TrpA1. Altogether, our results demonstrate the essential roles of the gut-peptide hormone AstA in mediating SD-associated energy wasting. [ABSTRACT FROM AUTHOR]

Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application of high-dimensionality reduction/spatial clustering and histopathological annotation of matrix assisted laser desorption/ionization imaging datasets to assess tissue metabolic heterogeneity in human lung diseases. Using metabolic features identified from this pipeline, we hypothesize that metabolic channeling between glycogen and N-linked glycans is a critical metabolic process favoring pulmonary fibrosis progression. To test our hypothesis, we induced pulmonary fibrosis in two different mouse models with lysosomal glycogen utilization deficiency. Both mouse models displayed blunted N-linked glycan levels and nearly 90% reduction in endpoint fibrosis when compared to WT animals. Collectively, we provide conclusive evidence that lysosomal utilization of glycogen is required for pulmonary fibrosis progression. In summary, our study provides a roadmap to leverage spatial metabolomics to understand foundational biology in pulmonary diseases. Spatial metabolomics are used to describe the location and chemistry of small molecules involved in metabolic phenotypes. Here, Conroy et al. present a bioinformatic pipeline to analyze MALDI data and show that it can be used to identify actionable targets such as glycogen in fibrotic lungs of both human and mice. [ABSTRACT FROM AUTHOR]

Vegetative phase change in plants is regulated by a gradual decline in the level of miR156 and a corresponding increase in the expression of its targets, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes. Gibberellin (GA), jasmonic acid (JA), and cytokinin (CK) regulate vegetative phase change by affecting genes in the miR156-SPL pathway. However, whether other phytohormones play a role in vegetative phase change remains unknown. Here, we show that a loss-of-function mutation in the brassinosteroid (BR) biosynthetic gene, DWARF5 (DWF5), delays vegetative phase change, and the defective phenotype is primarily attributable to reduced levels of SPL9 and miR172, and a corresponding increase in TARGET OF EAT1 (TOE1). We further show that GLYCOGEN SYNTHASE KINASE3 (GSK3)-like kinase BRASSINOSTEROID INSENSITIVE2 (BIN2) directly interacts with and phosphorylates SPL9 and TOE1 to cause subsequent proteolytic degradation. Therefore, BRs function to stabilize SPL9 and TOE1 simultaneously to regulate vegetative phase change in plants. Zhou et al. reveal a novel role for brassinosteroids in regulation of vegetative phase change in Arabidopsis. Brassinosteroids regulate this process by simultaneously stabilizing SPL9 and TOE1 through the BIN2-mediated phosphorylation process. [ABSTRACT FROM AUTHOR]

Perisynaptic astrocytic processes involved in the tripartite synapse functioning respond to its activation by local depolarization with calcium ions release from the intracellular stores inside nodes of astrocytic processes and develop local or generalized calcium events. However, based on the first electron microscopy studies the opinion was formed that terminal astrocytic lamellae are devoid of any organelles, including the main astrocytic calcium store – the cisternae of the smooth endoplasmic reticulum. Indeed, the analysis of smooth endoplasmic reticulum cisternae could be limited by their weak electron contrast, the studying of astrocytic processes on single sections, and insufficient optical resolution of the equipment used. Here, using serial section transmission electron microscopy and 3D reconstructions, we analyzed astrocytic processes in murine hippocampal and cortical synapses. As a result of unit membranes contrast enhancement, it was shown for the first time that perisynaptic processes of astrocytes with a morphology of thin branchlets contained two types of smooth endoplasmic reticulum cisternae and microvesicles. Unlike branchlets, membranous organelles inside terminal lamellae were comprised by only short fragments of thin smooth endoplasmic reticulum cisternae and microvesicles, whose groups tended to be located in close proximity to active zones of the most active synapses. This paper discusses both the reliability of alternative electron microscopy methods while studying astrocytic microenvironment of synapses and structure-function aspects of smooth endoplasmic reticulum cisternae compartmentalization inside the perisynaptic processes of astrocytes. [ABSTRACT FROM AUTHOR]

The plasma membrane glucose transporter-2 (GLUT2) monitors brain cell uptake of the critical nutrient glucose, and functions within astrocytes of as-yet-unknown location to control glucose counter-regulation. Hypothalamic astrocyte-neuron metabolic coupling provides vital cues to the neural glucostatic network. Current research utilized an established hypothalamic primary astrocyte culture model along with gene knockdown tools to investigate whether GLUT2 imposes sex-specific regulation of glucose/energy sensor function and glycogen metabolism in this cell population. Data show that GLUT2 stimulates or inhibits glucokinase (GCK) expression in glucose-supplied versus -deprived male astrocytes, but does not control this protein in female. Astrocyte 5'-AMP-activated protein kinaseα1/2 (AMPK) protein is augmented by GLUT2 in each sex, but phosphoAMPKα1/2 is coincidently up- (male) or down- (female) regulated. GLUT2 effects on glycogen synthase (GS) diverges in the two sexes, but direction of this control is reversed by glucoprivation in each sex. GLUT2 increases (male) or decreases (female) glycogen phosphorylase-brain type (GPbb) protein during glucoprivation, yet simultaneously inhibits (male) or stimulates (female) GP-muscle type (GPmm) expression. Astrocyte glycogen accumulation is restrained by GLUT2 when glucose is present (male) or absent (both sexes). Outcomes disclose sex-dependent GLUT2 control of the astrocyte glycolytic pathway sensor GCK. Data show that glucose status determines GLUT2 regulation of GS (both sexes), GPbb (female), and GPmm (male), and that GLUT2 imposes opposite control of GS, GPbb, and GPmm profiles between sexes during glucoprivation. Ongoing studies aim to investigate molecular mechanisms underlying sex-dimorphic GLUT2 regulation of hypothalamic astrocyte metabolic-sensory and glycogen metabolic proteins, and to characterize effects of sex-specific astrocyte target protein responses to GLUT2 on glucose regulation. [ABSTRACT FROM AUTHOR]

Glycogen, amino acids, fatty acids, and other nutrient components affect the flavor and nutritional quality of oysters. Methods based on near-infrared reflectance spectroscopy (NIRS) were developed to rapidly and proximately determine the nutrient content of the Pacific oyster Crassostrea gigas. Samples of C. gigas from 19 costal sites were freeze-dried, ground, and scanned for spectral data collection using a Fourier transform NIR spectrometer (Thermo Fisher Scientific). NIRS models of glycogen and other nutrients were established using partial least squares, multiplication scattering correction, first-order derivation, and Norris smoothing. The RC values of the glycogen, fatty acids, amino acids, and taurine NIRS models were 0.967 8, 0.931 2, 0.913 2, and 0.892 8, respectively, and the residual prediction deviation (RPD) values of these components were 3.15, 2.16, 3.11, and 1.59, respectively, indicating a high correlation between the predicted and observed values, and that the models can be used in practice. The models were used to evaluate the nutrient compositions of 1 278 oyster samples. Glycogen content was found to be positively correlated with fatty acids and negatively correlated with amino acids. The glycogen, amino acid, and taurine levels of C. gigas cultured in the subtidal and intertidal zones were also significantly different. This study suggests that C. gigas NIRS models can be a cost-effective alternative to traditional methods for the rapid and proximate analysis of various slaughter traits and may also contribute to future genetic and breeding-related studies in Pacific oysters. [ABSTRACT FROM AUTHOR]

Cyanobacteria accumulate polyglucan as main carbohydrate storage. Here, the cellular polyglucan content was determined in 27 cyanobacterial strains from 25 genera. The polyglucan contents were significantly enhanced in 20 and 23 strains under nitrogen (–N) and phosphate (–P) deprivation, respectively. High polyglucan accumulation was not associated with particular evolutionary groups but was strain specific. The highest polyglucan accumulations of 46.2% and 52.5% (w/w dry weight; DW) were obtained under –N in Synechocystis sp. PCC 6803 (hereafter Synechocystis) and Chroococcus limneticus, respectively. In Synechocystis, 80–97% (w/w) of the polyglucan was glycogen. Transcriptome and metabolome analyses during glycogen accumulation under –N were determined in Synechocystis. The genes responsible for the supply of the substrates for glycogen synthesis: glycerate-1,3-phosphate and fructose-1,6-phosphate, were significantly up-regulated. The genes encoding the enzymes converting succinate to malate in TCA cycle, were significantly down-regulated. The genes encoding the regulator proteins which inhibits metabolism at lower part of glycolysis pathway, were also significantly up-regulated. The transcript levels of PII protein and the level of 2-oxoglutarate, which form a complex that inhibits lower part of glycolysis pathway, were significantly increased. Thus, the increased Synechocystis glycogen accumulation under –N was likely to be mediated by the increased supply of glycogen synthesis substrates and metabolic inhibitions at lower part of glycolysis pathway and TCA cycle. [ABSTRACT FROM AUTHOR]

Purpose: A prospective case–control study was conducted to evaluate glycogen deposition within the detrusor and its correlation with the urodynamic findings in patients with bladder outlet obstruction (BOO) due to benign prostate hyperplasia (BPH). Material and methods: Data from 50 patients with BPH (Study Group) and 20 controls (Control Group) were analyzed. BOO was confirmed by pressure-flow studies. The main outcome was glycogen deposition within the bladder wall. Bladder tissue biopsies were obtained from all patients, and histological assessment of the detrusor glycogen content was performed using Periodate Acid Schiff's (PAS) stain. The obtained glycogen score ranged from 0 (no staining of glycogen granules) to 3 (staining of glycogen granules within the detrusor adjacent to the urothelium). Results: Fifty patients and 20 controls were included. Increased glycogen deposition was observed in 37 (74%) and 2 (10%) patients in the Study and Control Group, respectively (p < 0.01, OR 25.6, 95% CI 5.2–125.8). In the subgroup analysis, no statistically significant difference was found between glycogen deposition score and IPSS, maximum detrusor pressure at maximum flow (PdetQmax) and duration of LUTS. In multivariate logistic regression, history of retention was the only variable which could predict high glycogen deposition (p = 0.019). Conclusions: Our results demonstrate increased detrusor glycogen deposition in patients with BOO due to BPH, but the amount of deposition did not seem to correlate with symptom severity and duration or urodynamic findings. [ABSTRACT FROM AUTHOR]

The Na+-K+-ATPase is a critical regulator of ion homeostasis during contraction, buffering interstitial K+ accumulation, which is linked to muscle fatigue during intense exercise. Within this context, we adopted a recently reported methodology to examine exercise-induced alterations in maximal Na+-K+-ATPase activity. Eighteen trained healthy young males completed a repeated high-intensity cycling protocol consisting of three periods (EX1-EX3) of intermittent exercise. Each period comprised 10 × 45-s cycling at ~ 105% Wmax and a repeated sprint test. Muscle biopsies were sampled at baseline and after EX3 for determination of maximal in vitro Na+-K+-ATPase activity. Blood was drawn after each period and in association with a 2-min cycling test at a standardized high intensity (~ 90% Wmax) performed before and after the session to assess plasma K+ accumulation. Further, a 5-h recovery period with the ingestion of carbohydrate or placebo supplementation was implemented to explore potential effects of carbohydrate availability before sampling a final biopsy and repeating all tests. A ~ 12% reduction in maximal Na+-K+-ATPase activity was demonstrated following EX3 compared to baseline (25.2 ± 3.9 vs. 22.4 ± 4.8 μmol·min−1·g−1 protein, P = 0.039), which was sustained at the recovery time point (~ 15% decrease compared to baseline to 21.6 ± 5.9 μmol·min−1·g−1 protein, P = 0.008). No significant effect of carbohydrate supplementation was observed on maximal Na+-K+-ATPase activity after recovery (P = 0.078). In conclusion, we demonstrate an exercise-induced depression of maximal Na+-K+-ATPase activity following high-intensity intermittent exercise, which was sustained during a 5-h recovery period and unrelated to carbohydrate availability under the present experimental conditions. This was shown using a novel NADH coupled assay and confirms previous findings using other methodological approaches. [ABSTRACT FROM AUTHOR]

Background: The growing interest in how exercise and carbohydrate (CHO) restriction may modify molecular responses that promote endurance adaptations has led to many interesting controversies.We conducted a systematic review and a meta-analysis regarding the effect of low-carbohydrate availability (LOW) pre-, during, or post-exercise, on the mRNA content of commonly measured genes involved in mitochondrial biogenesis (PGC-1α, TFAM mRNA) and metabolism (PDK4, UCP3 and GLUT4 mRNA), and on muscle glycogen levels, compared with a high-CHO (CON) condition.MEDLINE, Scopus, and Web of Science databases were searched following the PRISMA 2020 guidelines (with an end date of November 2023). In total, 19 randomized-controlled studies were considered for inclusion. We evaluated the methodological quality of all studies using the Cochrane Risk of Bias tool for randomized clinical studies. A meta-analysis was performed using a random effects model to calculate the standardized mean difference (SMD), estimated by Hedges’ g, and 95% confidence intervals (CIs).The LOW condition was associated with an increased mRNA content of several genes during the early recovery period post-exercise, such as PDK4 (SMD 1.61; 95% CI 0.80–2.42), GLUT4 (SMD 1.38; 95% CI 0.46–2.30), and UCP3 (SMD 2.05; 95% CI 0.40–3.69). However, overall, there was no significant effect on the mRNA content of PGC-1α or TFAM. Finally, CHO restriction and exercise significantly reduced muscle glycogen levels (SMD 3.69; 95% CI 2.82–5.09). A meta-analysis of subgroups from studies with a difference in muscle glycogen concentration of > 200 mmol kg dw−1 between the LOW and CON conditions showed an increase in exercise-induced PGC-1α mRNA (SMD 2.08; 95% CI 0.64–3.52; p = 0.005; I2 = 75%) and a greater effect in PDK4 and GLUT4 mRNA.The meta-analysis results show that CHO restriction was associated with an increase in the exercise-induced mRNA content of PDK4, UCP3, and GLUT4, but not the exercise-induced mRNA content of PGC-1ɑ and TFAM. However, when there were substantial differences in glycogen depletion between CON and LOW CHO conditions (> 200 mmol kg dw−1), there was a greater effect of CHO restriction on the exercise-induced mRNA content of metabolic genes, and an increase in exercise-induced PGC-1α mRNA.Objective: The growing interest in how exercise and carbohydrate (CHO) restriction may modify molecular responses that promote endurance adaptations has led to many interesting controversies.We conducted a systematic review and a meta-analysis regarding the effect of low-carbohydrate availability (LOW) pre-, during, or post-exercise, on the mRNA content of commonly measured genes involved in mitochondrial biogenesis (PGC-1α, TFAM mRNA) and metabolism (PDK4, UCP3 and GLUT4 mRNA), and on muscle glycogen levels, compared with a high-CHO (CON) condition.MEDLINE, Scopus, and Web of Science databases were searched following the PRISMA 2020 guidelines (with an end date of November 2023). In total, 19 randomized-controlled studies were considered for inclusion. We evaluated the methodological quality of all studies using the Cochrane Risk of Bias tool for randomized clinical studies. A meta-analysis was performed using a random effects model to calculate the standardized mean difference (SMD), estimated by Hedges’ g, and 95% confidence intervals (CIs).The LOW condition was associated with an increased mRNA content of several genes during the early recovery period post-exercise, such as PDK4 (SMD 1.61; 95% CI 0.80–2.42), GLUT4 (SMD 1.38; 95% CI 0.46–2.30), and UCP3 (SMD 2.05; 95% CI 0.40–3.69). However, overall, there was no significant effect on the mRNA content of PGC-1α or TFAM. Finally, CHO restriction and exercise significantly reduced muscle glycogen levels (SMD 3.69; 95% CI 2.82–5.09). A meta-analysis of subgroups from studies with a difference in muscle glycogen concentration of > 200 mmol kg dw−1 between the LOW and CON conditions showed an increase in exercise-induced PGC-1α mRNA (SMD 2.08; 95% CI 0.64–3.52; p = 0.005; I2 = 75%) and a greater effect in PDK4 and GLUT4 mRNA.The meta-analysis results show that CHO restriction was associated with an increase in the exercise-induced mRNA content of PDK4, UCP3, and GLUT4, but not the exercise-induced mRNA content of PGC-1ɑ and TFAM. However, when there were substantial differences in glycogen depletion between CON and LOW CHO conditions (> 200 mmol kg dw−1), there was a greater effect of CHO restriction on the exercise-induced mRNA content of metabolic genes, and an increase in exercise-induced PGC-1α mRNA.Methods: The growing interest in how exercise and carbohydrate (CHO) restriction may modify molecular responses that promote endurance adaptations has led to many interesting controversies.We conducted a systematic review and a meta-analysis regarding the effect of low-carbohydrate availability (LOW) pre-, during, or post-exercise, on the mRNA content of commonly measured genes involved in mitochondrial biogenesis (PGC-1α, TFAM mRNA) and metabolism (PDK4, UCP3 and GLUT4 mRNA), and on muscle glycogen levels, compared with a high-CHO (CON) condition.MEDLINE, Scopus, and Web of Science databases were searched following the PRISMA 2020 guidelines (with an end date of November 2023). In total, 19 randomized-controlled studies were considered for inclusion. We evaluated the methodological quality of all studies using the Cochrane Risk of Bias tool for randomized clinical studies. A meta-analysis was performed using a random effects model to calculate the standardized mean difference (SMD), estimated by Hedges’ g, and 95% confidence intervals (CIs).The LOW condition was associated with an increased mRNA content of several genes during the early recovery period post-exercise, such as PDK4 (SMD 1.61; 95% CI 0.80–2.42), GLUT4 (SMD 1.38; 95% CI 0.46–2.30), and UCP3 (SMD 2.05; 95% CI 0.40–3.69). However, overall, there was no significant effect on the mRNA content of PGC-1α or TFAM. Finally, CHO restriction and exercise significantly reduced muscle glycogen levels (SMD 3.69; 95% CI 2.82–5.09). A meta-analysis of subgroups from studies with a difference in muscle glycogen concentration of > 200 mmol kg dw−1 between the LOW and CON conditions showed an increase in exercise-induced PGC-1α mRNA (SMD 2.08; 95% CI 0.64–3.52; p = 0.005; I2 = 75%) and a greater effect in PDK4 and GLUT4 mRNA.The meta-analysis results show that CHO restriction was associated with an increase in the exercise-induced mRNA content of PDK4, UCP3, and GLUT4, but not the exercise-induced mRNA content of PGC-1ɑ and TFAM. However, when there were substantial differences in glycogen depletion between CON and LOW CHO conditions (> 200 mmol kg dw−1), there was a greater effect of CHO restriction on the exercise-induced mRNA content of metabolic genes, and an increase in exercise-induced PGC-1α mRNA.Results: The growing interest in how exercise and carbohydrate (CHO) restriction may modify molecular responses that promote endurance adaptations has led to many interesting controversies.We conducted a systematic review and a meta-analysis regarding the effect of low-carbohydrate availability (LOW) pre-, during, or post-exercise, on the mRNA content of commonly measured genes involved in mitochondrial biogenesis (PGC-1α, TFAM mRNA) and metabolism (PDK4, UCP3 and GLUT4 mRNA), and on muscle glycogen levels, compared with a high-CHO (CON) condition.MEDLINE, Scopus, and Web of Science databases were searched following the PRISMA 2020 guidelines (with an end date of November 2023). In total, 19 randomized-controlled studies were considered for inclusion. We evaluated the methodological quality of all studies using the Cochrane Risk of Bias tool for randomized clinical studies. A meta-analysis was performed using a random effects model to calculate the standardized mean difference (SMD), estimated by Hedges’ g, and 95% confidence intervals (CIs).The LOW condition was associated with an increased mRNA content of several genes during the early recovery period post-exercise, such as PDK4 (SMD 1.61; 95% CI 0.80–2.42), GLUT4 (SMD 1.38; 95% CI 0.46–2.30), and UCP3 (SMD 2.05; 95% CI 0.40–3.69). However, overall, there was no significant effect on the mRNA content of PGC-1α or TFAM. Finally, CHO restriction and exercise significantly reduced muscle glycogen levels (SMD 3.69; 95% CI 2.82–5.09). A meta-analysis of subgroups from studies with a difference in muscle glycogen concentration of > 200 mmol kg dw−1 between the LOW and CON conditions showed an increase in exercise-induced PGC-1α mRNA (SMD 2.08; 95% CI 0.64–3.52; p = 0.005; I2 = 75%) and a greater effect in PDK4 and GLUT4 mRNA.The meta-analysis results show that CHO restriction was associated with an increase in the exercise-induced mRNA content of PDK4, UCP3, and GLUT4, but not the exercise-induced mRNA content of PGC-1ɑ and TFAM. However, when there were substantial differences in glycogen depletion between CON and LOW CHO conditions (> 200 mmol kg dw−1), there was a greater effect of CHO restriction on the exercise-induced mRNA content of metabolic genes, and an increase in exercise-induced PGC-1α mRNA.Conclusion: The growing interest in how exercise and carbohydrate (CHO) restriction may modify molecular responses that promote endurance adaptations has led to many interesting controversies.We conducted a systematic review and a meta-analysis regarding the effect of low-carbohydrate availability (LOW) pre-, during, or post-exercise, on the mRNA content of commonly measured genes involved in mitochondrial biogenesis (PGC-1α, TFAM mRNA) and metabolism (PDK4, UCP3 and GLUT4 mRNA), and on muscle glycogen levels, compared with a high-CHO (CON) condition.MEDLINE, Scopus, and Web of Science databases were searched following the PRISMA 2020 guidelines (with an end date of November 2023). In total, 19 randomized-controlled studies were considered for inclusion. We evaluated the methodological quality of all studies using the Cochrane Risk of Bias tool for randomized clinical studies. A meta-analysis was performed using a random effects model to calculate the standardized mean difference (SMD), estimated by Hedges’ g, and 95% confidence intervals (CIs).The LOW condition was associated with an increased mRNA content of several genes during the early recovery period post-exercise, such as PDK4 (SMD 1.61; 95% CI 0.80–2.42), GLUT4 (SMD 1.38; 95% CI 0.46–2.30), and UCP3 (SMD 2.05; 95% CI 0.40–3.69). However, overall, there was no significant effect on the mRNA content of PGC-1α or TFAM. Finally, CHO restriction and exercise significantly reduced muscle glycogen levels (SMD 3.69; 95% CI 2.82–5.09). A meta-analysis of subgroups from studies with a difference in muscle glycogen concentration of > 200 mmol kg dw−1 between the LOW and CON conditions showed an increase in exercise-induced PGC-1α mRNA (SMD 2.08; 95% CI 0.64–3.52; p = 0.005; I2 = 75%) and a greater effect in PDK4 and GLUT4 mRNA.The meta-analysis results show that CHO restriction was associated with an increase in the exercise-induced mRNA content of PDK4, UCP3, and GLUT4, but not the exercise-induced mRNA content of PGC-1ɑ and TFAM. However, when there were substantial differences in glycogen depletion between CON and LOW CHO conditions (> 200 mmol kg dw−1), there was a greater effect of CHO restriction on the exercise-induced mRNA content of metabolic genes, and an increase in exercise-induced PGC-1α mRNA. [ABSTRACT FROM AUTHOR]

Red microalgae from the Cyanidiophyceae, particularly Galdieria sulphuraria and Cyanidioschyzon merolae, are primitive photosynthetic thermoacidophiles that thrive in acidic hot springs and geysers. Unlike most Cyanidiophyceae, Galdieria strains are metabolically flexible as they can switch from photoautotrophic growth in the light to heterotrophic growth in complete darkness. Galdieria sulphuraria is especially noteworthy for its accumulation of various commercially valuable, functional compounds such as glycogen and phycocyanin. Glycogen, a branched fractal-like polysaccharide composed of several thousands of anhydroglucopyranose units, can be added to cosmetic products and sports drinks as a moisturizer or slow-digestible carbohydrate. While the production and structural characteristics of the glycogen of G. sulphuraria 108.79, isolated from Yellowstone National Park, have been previously described, our investigation aimed to explore glycogen production and properties across various Galdieria strains from different locations. Our findings reveal that all examined strains produce substantial amounts of highly branched glycogen when grown heterotrophically on glycerol in the dark. Notably, the structural characteristics of Galdieria glycogen distinguish it from both eukaryotic and prokaryotic glycogen, exhibiting a significantly higher degree of branching, substantially shorter side chains, and a considerable extent of indigestibility. These findings support the hypothesis that this highly branched, small glycogen is a long-term energy store, enabling survival during extended periods of complete darkness. [ABSTRACT FROM AUTHOR]

Background: Multiple factors influence substrate oxidation during exercise including exercise duration and intensity, sex, and dietary intake before and during exercise. However, the relative influence and interaction between these factors is unclear. Objectives: Our aim was to investigate factors influencing the respiratory exchange ratio (RER) during continuous exercise and formulate multivariable regression models to determine which factors best explain RER during exercise, as well as their relative influence. Methods: Data were extracted from 434 studies reporting RER during continuous cycling exercise. General linear mixed-effect models were used to determine relationships between RER and factors purported to influence RER (e.g., exercise duration and intensity, muscle glycogen, dietary intake, age, and sex), and to examine which factors influenced RER, with standardized coefficients used to assess their relative influence. Results: The RER decreases with exercise duration, dietary fat intake, age, VO2max, and percentage of type I muscle fibers, and increases with dietary carbohydrate intake, exercise intensity, male sex, and carbohydrate intake before and during exercise. The modelling could explain up to 59% of the variation in RER, and a model using exclusively easily modified factors (exercise duration and intensity, and dietary intake before and during exercise) could only explain 36% of the variation in RER. Variables with the largest effect on RER were sex, dietary intake, and exercise duration. Among the diet-related factors, daily fat and carbohydrate intake have a larger influence than carbohydrate ingestion during exercise. Conclusion: Variability in RER during exercise cannot be fully accounted for by models incorporating a range of participant, diet, exercise, and physiological characteristics. To better understand what influences substrate oxidation during exercise further research is required on older subjects and females, and on other factors that could explain additional variability in RER. [ABSTRACT FROM AUTHOR]

The delicate alternation between glycogen synthesis and degradation is governed by the interplay between key regulatory enzymes altering the activity of glycogen synthase and phosphorylase. Among these, the PP1 phosphatase promotes glycogenesis while inhibiting glycogenolysis. PP1 is, however, a master regulator of a variety of cellular processes, being conveniently directed to each of them by scaffolding subunits. PTG, Protein Targeting to Glycogen, addresses PP1 action to glycogen granules. In Lafora disease, the most aggressive pediatric epilepsy, genetic alterations leading to PTG accumulation cause the deposition of insoluble polyglucosans in neurons. Here, we report the crystallographic structure of the ternary complex PP1/PTG/carbohydrate. We further refine the mechanism of the PTG-mediated PP1 recruitment to glycogen by identifying i) an unusual combination of recruitment sites, ii) their contributions to the overall binding affinity, and iii) the conformational heterogeneity of this complex by in solution SAXS analyses. Glycogen metabolism is tightly regulated. Here the authors describe the 3D structure of the PP1/PTG protein complex, which plays a prominent role in the activation of glycogen synthesis and in the pathogenesis of Lafora disease, the most severe form of pediatric progressive epilepsy. [ABSTRACT FROM AUTHOR]

Streptomyces are our principal source of antibiotics, which they generate concomitant with a complex developmental transition from vegetative hyphae to spores. c-di-GMP acts as a linchpin in this transition by binding and regulating the key developmental regulators, BldD and WhiG. Here we show that c-di-GMP also binds the glycogen-debranching-enzyme, GlgX, uncovering a direct link between c-di-GMP and glycogen metabolism in bacteria. Further, we show c-di-GMP binding is required for GlgX activity. We describe structures of apo and c-di-GMP-bound GlgX and, strikingly, their comparison shows c-di-GMP induces long-range conformational changes, reorganizing the catalytic pocket to an active state. Glycogen is an important glucose storage compound that enables animals to cope with starvation and stress. Our in vivo studies reveal the important biological role of GlgX in Streptomyces glucose availability control. Overall, we identify a function of c-di-GMP in controlling energy storage metabolism in bacteria, which is widespread in Actinobacteria. c-di-GMP has emerged as the signal controlling development in antibiotic producing Streptomyces. Here the authors describe another developmental role of c-di-GMP, in energy metabolism, by activating the glycogen-debranchingenzyme, GlgX. Structures revealing the activation mechanism are described. [ABSTRACT FROM AUTHOR]

Exercise has been shown to increase growth of many salmonid species. However, limited research has evaluated exercise on warmwater species. The present study was conducted to evaluate with tilapia, red drum (RD), and hybrid striped bass (HSB), the effects of swimming (exercising) in a constant slow current of approximately one body length/s (1bl/s) compared to not being forced to swim in a static culture system. Concurrent trials were conducted with 22 advanced juvenile male Nile tilapia (Wt0 97.9 ± 2.4 g), 38 juvenile red drum (Wt0 74.9 ± 4.4 g), and 20 juvenile HSB (Wt0 78.0 ± 3.2 g). Equal numbers of fish of each species were pit tagged and randomly assigned to two tanks, one operated static (control) and the other with current (exercised), which were all part of the same recirculating aquaculture system. Fish were fed to satiation twice daily a commercial diet and individually weighed every 2 weeks through 7 weeks. Significant (P ≤ 0.05) enhancements of weight gain were observed for exercised tilapia and RD vs static (control) treatments. Reduced growth was observed in exercised HSB, possibly due to consistently skittish feeding behavior. Hepatosomatic index was lower in all exercised fish, though not significantly so for RD and tilapia. Significant reductions also were detected in liver glycogen of exercised tilapia and RD. Results from this study indicate that continuous exercise beneficially affected aspects of tilapia and red drum growth and altered their body composition. [ABSTRACT FROM AUTHOR]

Photoperiod is a key environmental indicator for regulating embryonic development, individual growth and physiological processes in aquatic animals. In this study, differences in embryonic development and performance of newly hatched cuttlefish juvenile exposed to five different cycles of lightdark (L:D): constant light, 18L:6D, 12L:12D, 6L:18D cycles, and constant darkness were evaluated. Prolonged exposure to light induced an accelerated rate of embryonic development, particularly after the red-bead stage. Principal component analysis (PCA) revealed that red-bead stage, heartbeat, endoskeleton formation, pigment appear, and six increments of cuttlebone were the main factors contributing to the embryonic development. Meaning that the duration time of these five stages were significantly different when exposed to photoperiod regimes, which may determine the duration of the incubation period of the embryos. Long term light has also affected the incubation parameters with an increased rate in hatching and shortened the incubation and hatching periods in the 12–24-h day length range. However, constant light and darkness environment appeared to have a greater effect on the stress of embryonic development, mainly reflected in the yolk shed ratio and the inking rate in the egg capsule. Moreover, the increase in the day length has contributed to improve the growth and survival of juveniles in the 12–18-h day length range; however, juveniles exposed to constant light and darkness experienced worse results in terms of growth, tissue glycogen content, digestive enzymes of the digestive glands, and metabolic enzymes of the muscles. These finding suggest that prolonged light exposure accelerates the process of embryonic development, maximum feeding time is not necessarily a condition of optimal growth, and inappropriate light cycles can disturb the body's endogenous controls. Therefore, the optimal photoperiod for the embryos development and juvenile growth of Sepia pharaonis were 12 h and 12–18 h of day length, respectively. These results are useful for increasing the production of this species during embryo incubation and juveniles rearing in aquaculture practice. [ABSTRACT FROM AUTHOR]

Purpose: Little progress has been made in understanding the effect of Trypanosoma brucei brucei infection that was allowed to run its course without treatment on human and animal carbohydrate metabolism even though most of the symptoms associated with the disease can be clearly linked with interference with host energy generation. The present study therefore assessed the course of untreated Trypanosoma brucei brucei infection on hepatic glycogen, hepatic hexokinase and glucokinase activities. Methods: Mice were grouped into two: control and infected group. Trypanosomiasis was induced by intraperitoneal inoculation of 1 × 104 parasites/mice in 0.3 ml of phosphate saline glucose. The infection was allowed to run its course until the first mortality was recorded with all the mice showing chronic symptoms of the second stage of the disease before the research was terminated. Blood and liver samples were collected from the mice in each group for the assessment of hepatic glycogen and total protein, hepatic hexokinase and glucokinase activities, liver biomarkers, blood glucose and protein with packed cell volume. Results: The infection resulted in decrease in blood glucose, hepatic glycogen, liver protein, PCV, hepatic hexokinase and glucokinase activities, but increase in serum total protein and liver biomarkers. Conclusion: Trypanosomiasis negatively affects hepatic integrity, resulting in the depletion of hepatic glycogen content and suppression of both hepatic hexokinase and glucokinase activities. The suppression of hepatic hexokinase and glucokinase activities suggested that trypanosomiasis affected the oxidation of glucose and host energy generation via glycolysis. This probably denied the host of the needed energy which is likely the reason for early death in untreated African trypanosomiasis. [ABSTRACT FROM AUTHOR]