Search

Introduction Testosterone (T) and 17[beta]-estradiol ([E.sub.2]) are considered male and female sex hormones, respectively, because they are secreted by gonads in the circulation at sex-specific concentrations and are involved in [...], Testosterone (T) and 17[beta]-estradiol ([E.sub.2]) are produced in male and female humans and are potent metabolic regulators in both sexes. When [E.sub.2] and T production stops or decreases during aging, metabolic dysfunction develops and promotes degenerative metabolic and vascular disease. Here, we discuss the shared benefits afforded by [E.sub.2] and T for metabolic function human females and males. In females, [E.sub.2] is central to bone and vascular health, subcutaneous adipose tissue distribution, skeletal muscle insulin sensitivity, antiinflammatory immune function, and mitochondrial health. However, T also plays a role in female skeletal, vascular, and metabolic health. In males, T's conversion to [E.sub.2] is fundamental to bone and vascular health, as well as prevention of excess visceral adiposity and the promotion of insulin sensitivity via activation of the estrogen receptors. However, T and its metabolite dihydrotestosterone also prevent excess visceral adiposity and promote skeletal muscle growth and insulin sensitivity via activation of the androgen receptor. In conclusion, T and [E.sub.2] are produced in both sexes at sex-specific concentrations and provide similar and potent metabolic benefits. Optimizing levels of both hormones may be beneficial to protect patients from cardiometabolic disease and frailty during aging, which requires further study.

Background Frozen embryo transfer (FET) has become a widely employed assisted reproductive technology technique. There have historically been concerns regarding the long-term metabolic safety of FET technology in offspring due to pregnancy-induced hypertension and large for gestational age, both of which are well-recognized factors for metabolic dysfunction of children. Therefore, we aimed to compare the metabolic profiles of children born after frozen versus fresh embryo transfer at 2 to 5 years of age. Methods and findings This was a prospective cohort study. Using data from the 'Assisted Reproductive Technology borned KIDs (ARTKID),' a birth cohort of offspring born from assisted reproductive technology at the Institute of Women, Children and Reproductive Health, Shandong University, China. We included 4,246 singletons born after FET (n = 2,181) and fresh embryo transfer (n = 2,065) enrolled between 2008 and 2019 and assessed the glucose and lipid variables until the age of 2 to 5 years. During a mean follow-up of 3.6 years, no significant differences were observed in fasting blood glucose, fasting insulin, Homeostatic Model Assessment of Insulin Resistance Index, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol levels between offspring conceived by fresh and frozen embryo transfer in the crude model and adjusted model (adjusted for parental age, parental body mass index, parental education level, paternal smoking, parity, offspring age and sex). These results remained consistent across subgroup analyses considering offspring age, the stage of embryo transfer, and the mode of fertilization. Results from sensitivity analysis on children matched for age within the cohort remains the same. The main limitation of our study is the young age of the offspring. Conclusions In this study, the impact of FET on glucose and lipid profiles during early childhood was comparable to fresh embryo transfer. Long-term studies are needed to evaluate the metabolic health of offspring born after FET., Author(s): Wei Zhou 1,2,3,4,5,6,7, Wanbing Feng 1,2,3,4,5,6,7, Jinli Chang 1,2,3,4,5,6,7, Jingmei Hu 1,2,3,4,5,6,7, Fuxia Li 1,2,3,4,5,6,7, Kuona Hu 1,2,3,4,5,6,7, Jiejing Jiao 1,2,3,4,5,6,7, Xinyi Xue 1,2,3,4,5,6,7, Ting Lan 1,2,3,4,5,6,7, Wenjing Wan [...]

The energetic consequences of body size, behaviour, and fine-scale environmental variation remain understudied, particularly among free-ranging carnivores, due to logistical and methodological challenges of studying them in the field. Here, we present novel activity, heart rate, and metabolic data on free-ranging Canada lynx (Lynx canadensis Kerr, 1792) to (i) investigate intraspecific patterns of energy expenditure, particularly how they relate to body size, environmental conditions, and activity variation, and (ii) position lynx - a cold-climate, mesocarnivore - within interspecific allometries of carnivore energetics. Lynx demonstrated limited behavioural and metabolic responses to environmental conditions, despite extreme cold and moderate snow depths during our study, but marked body size patterns with larger lynx having higher activity and lower resting heart rate than smaller lynx. Compared with similar-sized carnivores, lynx were less active and had lower heart rate, likely due to their ambush hunting style, but higher energy expenditure, likely due to their coldclimate existence and access to abundant prey. Overall, lynx were more similar to other ambush hunters than to sympatric cold-climate species and mesocarnivores. Our data provide insight into the relative importance of abiotic and biotic drivers of carnivore energetics and the ways in which predators maintain energy balance in variable environments. Key words: activity, allometry, biologger, boreal ecology, energy expenditure, heart rate, Canada lynx, Lynx canadensis, mesocarnivore, winter. Les consequences energetiques de la taille du corps, du comportement et de variations environnementales a petite echelle demeurent sous-etudiees, particulierement chez les carnivores en liberte en raison de defis logistiques et methodologiques associes a leur etude sur le terrain. Nous presentons de nouvelles donnees sur l'activite, le rythme cardiaque et le metabolisme pour des lynx du Canada (Lynx canadensis Kerr, 1792) en liberte afin (i) d'examiner les motifs intraspecifiques de depense d'energie, plus particulierement leurs relations a la taille du corps, aux conditions ambiantes et aux variations de l'activite, et (ii) de positionner le lynx, un mesocarnivore de climat froid, au sein d'allometries interspecifiques d'energetique des carnivores. Les lynx presentent des reactions comportementales et metaboliques limitees aux conditions ambiantes, malgre des froids extremes et des epaisseurs de neige moderees durant l'etude, mais des motifs de taille du corps marques, les plus grands lynx presentant une plus grande activite et un rythme cardiaque au repos plus faible que les lynx plus petits. Comparativement a d'autres carnivores de taille semblable, les lynx etaient moins actifs et leur rythme cardiaque etait plus faible, probablement en raison de leur mode de chasse par embuscade, mais de plus grandes depenses energetiques, vraisemblablement en raison de leur vie en climat froid et leur acces a une abondance de proies. Globalement, les lynx sont plus semblables a d'autres chasseurs par embuscade qu'a des especes sympatriques et des mesocarnivores de climat froid. Nos donnees permettent de mieux comprendre l'importance relative de facteurs abiotiques et biotiques qui influencent l'energetique des carnivores et les moyens qu'emploient les predateurs pour maintenir leur equilibre energetique dans des milieux variables. [Traduit par la Redaction] Mots-cles : activite, allometrie, capteur de parametres biologiques, ecologie boreale, depense energetique, rythme cardiaque, lynx du Canada, Lynx canadensis, mesocarnivore, hiver., Introduction Predators occupying high trophic positions tend to have high energy requirements due to their large body size (Kleiber 1932; Schmidt-Nielsen 1984; Peters 1986; White et al. 2019); elevated resting [...]

Adipocytes increase energy expenditure in response to prolonged sympathetic activation via persistent expression of uncoupling protein 1 (UCP1).sup.1,2. Here we report that the regulation of glycogen metabolism by catecholamines is critical for UCP1 expression. Chronic [beta]-adrenergic activation leads to increased glycogen accumulation in adipocytes expressing UCP1. Adipocyte-specific deletion of a scaffolding protein, protein targeting to glycogen (PTG), reduces glycogen levels in beige adipocytes, attenuating UCP1 expression and responsiveness to cold or [beta]-adrenergic receptor-stimulated weight loss in obese mice. Unexpectedly, we observed that glycogen synthesis and degradation are increased in response to catecholamines, and that glycogen turnover is required to produce reactive oxygen species leading to the activation of p38 MAPK, which drives UCP1 expression. Thus, glycogen has a key regulatory role in adipocytes, linking glucose metabolism to thermogenesis. Increased glycogen metabolism in adipocytes leads to expression of uncoupling protein 1, thereby linking glucose metabolism to thermogenesis., Author(s): Omer Keinan [sup.1] , Joseph M. Valentine [sup.1] , Haopeng Xiao [sup.2] [sup.3] , Sushil K. Mahata [sup.4] , Shannon M. Reilly [sup.1] , Mohammad Abu-Odeh [sup.1] , Julia [...]

The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements were available. We found many significant associations between microbes and specific nutrients, foods, food groups and general dietary indices, which were driven especially by the presence and diversity of healthy and plant-based foods. Microbial biomarkers of obesity were reproducible across external publicly available cohorts and in agreement with circulating blood metabolites that are indicators of cardiovascular disease risk. While some microbes, such as Prevotella copri and Blastocystis spp., were indicators of favorable postprandial glucose metabolism, overall microbiome composition was predictive for a large panel of cardiometabolic blood markers including fasting and postprandial glycemic, lipemic and inflammatory indices. The panel of intestinal species associated with healthy dietary habits overlapped with those associated with favorable cardiometabolic and postprandial markers, indicating that our large-scale resource can potentially stratify the gut microbiome into generalizable health levels in individuals without clinically manifest disease. Analyses from the gut microbiome of over 1,000 individuals from the PREDICT 1 study, for which detailed long-term diet information as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements are available, unveil new associations between specific gut microbes, dietary habits and cardiometabolic health., Author(s): Francesco Asnicar [sup.1] , Sarah E. Berry [sup.2] , Ana M. Valdes [sup.3] [sup.4] , Long H. Nguyen [sup.5] , Gianmarco Piccinno [sup.1] , David A. Drew [sup.5] , [...]

Cancer cells exhibit altered and usually increased metabolic processes to meet their high biogenetic demands.sup.1,2. Under these conditions, ammonia is concomitantly produced by the increased metabolic processing. However, it is unclear how tumour cells dispose of excess ammonia and what outcomes might be caused by the accumulation of ammonia. Here we report that the tumour suppressor p53, the most frequently mutated gene in human tumours, regulates ammonia metabolism by repressing the urea cycle. Through transcriptional downregulation of CPS1, OTC and ARG1, p53 suppresses ureagenesis and elimination of ammonia in vitro and in vivo, leading to the inhibition of tumour growth. Conversely, downregulation of these genes reciprocally activates p53 by MDM2-mediated mechanism(s). Furthermore, the accumulation of ammonia causes a significant decline in mRNA translation of the polyamine biosynthetic rate-limiting enzyme ODC, thereby inhibiting the biosynthesis of polyamine and cell proliferation. Together, these findings link p53 to ureagenesis and ammonia metabolism, and further reveal a role for ammonia in controlling polyamine biosynthesis and cell proliferation. p53 regulates the metabolism of ammonia by repressing genes of the urea cycle that function to eliminate excess ammonia., Author(s): Le Li [sup.1] , Youxiang Mao [sup.1] , Lina Zhao [sup.1] , Lijia Li [sup.1] , Jinjun Wu [sup.1] , Mengjia Zhao [sup.1] , Wenjing Du [sup.2] , Li [...]

Author(s): Steven B. Heymsfield [sup.1] Author Affiliations: (1) Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, USA Introduction What do the following three equations for predicting resting energy expenditure [...]

Due to their daily involvement in mineral metabolism, nephrologists are often asked to consult on children with hypercalcemia. This might become even more pertinent when the hypercalcemia is associated with acute kidney injury and/or hypercalciuria and renal calcifications. The best way to assess the severity of hypercalcemia is by measurement of plasma ionized calcium, and if not available by adjusting serum total calcium to albumin concentration. The differential diagnosis of the possible etiologies of the disturbance in the mineral homeostasis starts with the assessment of serum parathyroid hormone concentration, followed by that of vitamin D metabolites in search of both genetic and acquired etiologies. Several tools are available to acutely treat hypercalcemia with the current main components being fluids, loop diuretics, and antiresorptive agents. This review will address the pathophysiologic mechanisms, clinical manifestations, and treatment modalities involved in hypercalcemia., Author(s): Ari Auron [sup.1] , Uri S. Alon [sup.1] Author Affiliations: (Aff1) 0000 0001 2179 926X, grid.266756.6, Bone and Mineral Disorders Clinic, Division of Pediatric Nephrology, Children's Mercy Hospital, University [...]

In the brain, the ventral hypothalamus (VHT) regulates energy and bone metabolism. Whether this regulation uses the same or different neuronal circuits is unknown. Alteration of AP1 signaling in the VHT increases energy expenditure, glucose utilization, and bone density, yet the specific neurons responsible for each or all of these phenotypes are not identified. Using neuron-specific, genetically targeted API alterations as a tool in adult mice, we found that agouti- related peptide-expressing (AgRP-expressing) or proopiomelanocortin-expressing (POMC-expressing) neurons, predominantly present in the arcuate nucleus (ARC) within the VHT, stimulate whole-body energy expenditure, glucose utilization, and bone formation and density, although their effects on bone resorption differed. In contrast, API alterations in steroidogenic factor 1-expressing (SFI-expressing) neurons, present in the ventromedial hypothalamus (VMH), increase energy but decrease bone density, suggesting that these effects are independent. Altered API signaling also increased the level of the neuromediator galanin in the hypothalamus. Global galanin deletion (VHT galanin silencing using shRNA) or pharmacological galanin receptor blockade counteracted the observed effects on energy and bone. Thus, API antagonism reveals that AgRP- and POMC-expressing neurons can stimulate body metabolism and increase bone density, with galanin acting as a central downstream effector. The results obtained with SFI-expressing neurons, however, indicate that bone homeostasis is not always dictated by the global energy status, and vice versa., Introduction The hypothalamus plays a central role in the systemic regulation of energy homeostasis (1). Several hypothalamic sites sense nutrient (e.g., glucose, lipids) and endocrine (e.g., leptin, insulin, ghrelin) cues [...]

Introduction Several studies have shown a strong correlation between the serum vitamin D level and asthma severity and deficits in lung function. Objective Study the relationship between vitamin D and the severity of asthma by targeting five SNPs of vitamin D metabolism gene pathway in a Tunisian adult asthmatics population. Methods Our case-control study includes 154 adult asthmatic patients and 154 healthy Tunisian subjects. We genotyped many variants in three human genes encoding key components of the vitamin D metabolism, CYP2R1, CYP27B1, GC. The GC gene rs4588 and rs7041 polymorphisms were analysed using the PCR-RFLP method, while rs10741657 and rs12794714 for CYP2R1 gene and rs10877012 of CYP27B1 gene were investigated using TaqMan PCR genotyping techniques. Results We found that the presence of at least one copy of the rs12794714 A, allele was associated with lower risk of developing asthma (OR 0.61). Further, the rs12794714 is a protector factor against asthma severity (OR 0.5). However, the presence of rs10877012 TG genotype is a risk factor related to asthma severity (OR 1.89). When we classified the population according to sex, our results showed that rs10877012 TT genotype was a risk factor for women subjects (OR 6.7). Moreover, the expression of TT genotype was associated with a higher risk of asthma in non-smoker patients (OR 7.13). We found a significant lower VD serum levels in asthmatics than controls but no impact of the polymorphisms on VD levels. Conclusions We found that rs12794714 and rs10877012 SNPs were associated with asthma risk., Author(s): Oussama Lahmar [sup.1] [sup.6] , Mariem Salhi [sup.1] , Wajih Kaabachi [sup.2] , Anissa Berraies [sup.3] , Jamel Ammar [sup.3] , Munawar Hussain Soomro [sup.4] , Martin Larsen [sup.5] [...]

Limiting dysfunctional neutrophilic inflammation while preserving effective immunity requires a better understanding of the processes that dictate neutrophil function in the tissues. Quantitative mass-spectrometry identified how inflammatory murine neutrophils regulated expression of cell surface receptors, signal transduction networks, and metabolic machinery to shape neutrophil phenotypes in response to hypoxia. Through the tracing of labeled amino acids into metabolic enzymes, proinflammatory mediators, and granule proteins, we demonstrated that ongoing protein synthesis shapes the neutrophil proteome. To maintain energy supplies in the tissues, neutrophils consumed extracellular proteins to fuel central carbon metabolism. The physiological stresses of hypoxia and hypoglycemia, characteristic of inflamed tissues, promoted this extracellular protein scavenging with activation of the lysosomal compartment, further driving exploitation of the protein-rich inflammatory milieu. This study provides a comprehensive map of neutrophil proteomes, analysis of which has led to the identification of active catabolic and anabolic pathways that enable neutrophils to sustain synthetic and effector functions in the tissues., Introduction The rapid recruitment of innate immune cells is critical for containing and eradicating infection and the restoration of normal tissue homeostasis. To enable effective immune responses in the tissues, [...]

Early life forms established a network of reactions for converting carbon dioxide into organic compounds. A non-biological system of reactions that could have formed the network's core on ancient Earth has been reported. A reaction network that might have contributed to the emergence of life., Author(s): Robert Pascal Author Affiliations: A possible non-biological reaction framework for metabolic processes on early Earth All biological molecules used by living organisms are themselves synthesized by living organisms. The [...]

Background Variability in measures of mineral metabolism has not been studied in pediatric end stage kidney disease. We sought to determine the intra-individual variability in measures of mineral metabolism in children on hemodialysis (HD) and its impact on clinical decision-making. Methods We conducted a prospective single-center study of children (3.6-17.3 years old) on chronic HD. Serial twice weekly measures of serum calcium, phosphate and intact parathyroid hormone (PTH), as well as weekly measures of fibroblast growth factor 23 (FGF23) and vitamin D metabolites, were obtained over a 12-week period in 10 children. Samples (n = 226) were assayed in a single batch at the end of the study. Results The median intra-individual coefficient of variation (CV) calculated by 4-week blocks was 5.1-6.5% for calcium, 9.5-14.9% for phosphate and 32.7-33.4% for PTH. The median overall CV for FGF23 was 44.4%. Using the first value of each block as a reference, subsequent values would dictate a discrepant management decision 33-56%, 19-28%, and 30-33% of the time for calcium, phosphate, and PTH, respectively. Adjusting for sex and age, most of the variability in phosphate and PTH was attributable to within-participant variability. For calcium, 49% of the variability was attributable to day of blood collection (Monday vs. Friday). The median (range) of an individual participant's values within clinical target ranges was 55% (26-86%) for calcium, 58% (0-96%) for phosphate, and 21% (0-64%) for PTH. Conclusions There is considerable intra-individual variability in measures of mineral metabolism that serve as surrogate markers for bone health in children on HD. Within a 4-week period, at least 20-30% of measures would dictate a discrepant decision from the referent measure of that month. These findings have important implications for clinical decision-making and underscore the need to base therapeutic decisions on trends rather than single measurements., Author(s): Aadil Kakajiwala [sup.1] [sup.2] , Thomas O. Jemielita [sup.3] , Lawrence Copelovitch [sup.2] [sup.4] , Mary B. Leonard [sup.5] , Susan L. Furth [sup.2] [sup.3] [sup.4] , Amy York [...]

Standard metabolic rates (SMR) were measured in brown bullheads (Ameiurus nebulosus) collected from two locations of the Detroit River, North America, representative of highly contaminated and uncontaminated areas. Measurements of SMR were completed within 10 days of fish collections (acute trials), for fish held in a common pond environment for 1 year (clearance trials) and for F1 generation fish raised in the pond environment ([F.sub.1] study). SMRs were significantly higher (26%) in fish from the contaminated area during acute trials. Both populations showed large decreases in SMR (49% to 52%) following clearance; however, differences between populations were still evident. There were no significant differences in SMRs between populations for [F.sub.1] fish. This study demonstrates that Detroit River brown bullheads from contaminated areas have higher metabolic rates than fish from clean locations, and this metabolic effect is retained for long durations after fish are placed in a common environment. The loss of metabolic differences in [F.sub.1] offspring indicates that the observed differences in SMR were acclimation-based and not adaptive or related to maternal effects. Le metabolisme standard (MS) a ete mesure sur des barbottes (Ameiurus nebulosus) prelevees de deux emplacements le long de la riviere Detroit (Amerique du Nord) representatifs de zones tres contaminees et non contaminees, respectivement. Des mesures du MS ont ete realisees dans les 10 jours suivant le prelevement des poissons (essais aigus), pour des poissons maintenus dans un milieu d'etang commun pendant un an (essais de clairance) et pour des poissons de la generation [F.sub.1] eleves dans le milieu d'etang (etude de la FJ. Le MS etait significativement plus eleve (26 %) chez les poissons issus de la zone contaminee durant les essais aigus. Les deux populations presentaient d'importantes diminutions du MS (de 49 % a 52 %) apres la periode de clairance, bien que des differences entre les populations fussent encore presentes. Aucune difference significative n'etait presente sur le plan du MS entre les deux populations pour les poissons Ft. L'etude demontre que les barbottes de la riviere Detroit issues de zones contaminees ont un metabolisme plus eleve que les poissons de zones non contaminees, et que cet effet metabolique est maintenu longtemps apres que les poissons aient ete places dans un milieu commun. La disparition des differences metaboliques chez la progeniture [F.sub.1] indique que les differences de MS observees sont le fait d'une acclimatation, non de l'adaptation ou reliees a des effets maternels. [Traduit par la Redaction], Introduction Standard metabolic rate (SMR) is an important component of the energy budget and represents the minimal energy required to sustain physiological function excluding consumption, digestion, and activity (Enders et [...]

Activation of glucose-sensing neurons in the ventromedial hypothalamic nucleus using radio waves or magnetic fields remotely and non-invasively in vivo increases plasma glucose and glucagon, and suppresses plasma insulin; conversely, remote inhibition of glucose-sensing neurons decreased blood glucose and increased plasma insulin. Remote control of animal behaviour This study describes a new technology that allows neurons to be activated or inhibited remotely in freely moving animals using radio waves or magnetic fields. Jeffrey Friedman and colleagues used an iron-binding protein tethered to a heat-sensitive protein to excite or inhibit neurons in the ventromedial hypothalamic nucleus in mice. Activation of glucose-sensing neurons increased plasma glucose and glucagon, suppressed plasma insulin and increased feeding. Inhibition decreased blood glucose, increased plasma insulin and suppressed the response to hypoglycaemia. As well as enabling remote control of cellular activity in basic research, this approach has potential therapeutic implications as a minimally invasive alternative to deep brain stimulation. Targeted, temporally regulated neural modulation is invaluable in determining the physiological roles of specific neural populations or circuits. Here we describe a system for non-invasive, temporal activation or inhibition of neuronal activity in vivo and its use to study central nervous system control of glucose homeostasis and feeding in mice. We are able to induce neuronal activation remotely using radio waves or magnetic fields via Cre-dependent expression of a GFP-tagged ferritin fusion protein tethered to the cation-conducting transient receptor potential vanilloid 1 (TRPV1) by a camelid anti-GFP antibody (anti-GFP-TRPV1).sup.1. Neuronal inhibition via the same stimuli is achieved by mutating the TRPV1 pore, rendering the channel chloride-permeable. These constructs were targeted to glucose-sensing neurons in the ventromedial hypothalamus in glucokinase-Cre mice, which express Cre in glucose-sensing neurons.sup.2. Acute activation of glucose-sensing neurons in this region increases plasma glucose and glucagon, lowers insulin levels and stimulates feeding, while inhibition reduces blood glucose, raises insulin levels and suppresses feeding. These results suggest that pancreatic hormones function as an effector mechanism of central nervous system circuits controlling blood glucose and behaviour. The method we employ obviates the need for permanent implants and could potentially be applied to study other neural processes or used to regulate other, even dispersed, cell types., Author(s): Sarah A. Stanley [sup.1] , Leah Kelly [sup.1] , Kaamashri N. Latcha [sup.1] , Sarah F. Schmidt [sup.1] , Xiaofei Yu [sup.1] , Alexander R. Nectow [sup.1] , Jeremy [...]

The transcription factor FOXO1 is identified as a crucial checkpoint of vascular growth, coupling the metabolic and proliferative activities of endothelial cells. FOXO1 is a checkpoint of vascular growth The mechanisms that balance the metabolism of endothelial cells and their growth state are not known. Here Michael Potente and colleagues identify the transcription factor FOXO1 as a crucial checkpoint of vascular growth, coupling the metabolic and proliferative activities of endothelial cells. They find that FOXO1 expression in endothelial cells is required to keep the cells quiescent, through suppressing c-MYC signalling, thereby reducing glycolysis and mitochondrial respiration. Endothelial-specific deletion of FOXO1 in mice induces vessel hyperplasia and enlargement. Endothelial cells (ECs) are plastic cells that can switch between growth states with different bioenergetic and biosynthetic requirements.sup.1. Although quiescent in most healthy tissues, ECs divide and migrate rapidly upon proangiogenic stimulation.sup.2,3. Adjusting endothelial metabolism to the growth state is central to normal vessel growth and function.sup.1,4, yet it is poorly understood at the molecular level. Here we report that the forkhead box O (FOXO) transcription factor FOXO1 is an essential regulator of vascular growth that couples metabolic and proliferative activities in ECs. Endothelial-restricted deletion of FOXO1 in mice induces a profound increase in EC proliferation that interferes with coordinated sprouting, thereby causing hyperplasia and vessel enlargement. Conversely, forced expression of FOXO1 restricts vascular expansion and leads to vessel thinning and hypobranching. We find that FOXO1 acts as a gatekeeper of endothelial quiescence, which decelerates metabolic activity by reducing glycolysis and mitochondrial respiration. Mechanistically, FOXO1 suppresses signalling by MYC (also known as c-MYC), a powerful driver of anabolic metabolism and growth.sup.5,6. MYC ablation impairs glycolysis, mitochondrial function and proliferation of ECs while its EC-specific overexpression fuels these processes. Moreover, restoration of MYC signalling in FOXO1-overexpressing endothelium normalizes metabolic activity and branching behaviour. Our findings identify FOXO1 as a critical rheostat of vascular expansion and define the FOXO1-MYC transcriptional network as a novel metabolic checkpoint during endothelial growth and proliferation., Author(s): Kerstin Wilhelm [sup.1] , Katharina Happel [sup.1] , Guy Eelen [sup.2] [sup.3] , Sandra Schoors [sup.2] [sup.3] , Mark F. Oellerich [sup.1] , Radiance Lim [sup.1] , Barbara Zimmermann [...]

The blue mussel (Mytilus edulis) has recently expanded its northern distribution in the Arctic and is therefore considered to be a sensitive indicator of climate changes in this region. In this study, we compared aerobic performance of blue mussels from High Arctic, Subarctic and temperate populations at different temperatures. Standard metabolic rates (SMR) and active metabolic rates (AMR) were measured for each population, and absolute (AMR - SMR) and factorial (AMR/SMR) scopes were calculated. Blue mussels from the temperate population had the lowest [Q1.sub.0] (= 1.8) and the largest thermal window (-1 to 25°C), whereas [Q.sub.10] values in the Arctic populations were 1.9 (Subarctic) and 2.3 (High Arctic), with a thermal window of -1 to 21°C. Aerobic scope increased with rising temperatures, reaching a maximum at 14°C (temperate) and 7°C (Subarctic and High Arctic, respectively), after which a decrease was observed at temperatures exceeding 14°C. At low temperatures (-1°C), the average SMR of the High Arctic population was 93 % higher than that of the temperate population and 22 % higher than that of the Subarctic population. Combined, our results demonstrate physiological adaptation and plasticity of blue mussels across latitudes spanning from 56 to 77°N. This indicates that low ocean temperature per se does not constrain metabolic activity of Mytilus in the Arctic; rather, we speculate that maturation of reproductive tissues, larval supply and annual energy budgets are the most relevant factors influencing Mytilus populations near their northern distributional edge in the Arctic., Introduction In the Arctic, recent ocean warming has occurred at a faster rate than the global average (Serreze et al. 2009). Warming of the oceans is affecting species distribution, genetics, [...]

Non-alcoholic fatty liver disease (NAFLD) is a broad spectrum liver disorder diagnosed in patients without a history of alcohol abuse. NAFLD is growing at alarming rates worldwide. Its pathogenesis is complex and incompletely understood. The cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) system regulates homocysteine and cysteine metabolism and contributes to endogenous hydrogen sulfide ([H.sub.2]S) biosynthesis. This review summarizes our current understanding of the hepatic CBS/CSE system, and for the first time, positions this system as a potential therapeutic target in NAFLD. As will be discussed, the CBS/CSE system is highly expressed and active in the liver. Its dysregulation, presenting as alterations in circulating homocysteine and (or) [H.sub.2]S levels, has been reported in NAFLD patients and in NAFLD-associated co-morbidities such as obesity and type 2 diabetes. Intricate links between the CBS/CSE system and a number of metabolic and stress related molecular mediators have also emerged. Various dysfunctions in the hepatic CBS/CSE system have been reported in animal models representative of each NAFLD spectrum. It is anticipated that a newfound appreciation for the hepatic CBS/CSE system will emerge that will improve our understanding of NAFLD pathogenesis, and give rise to new prospective targets for management of this disorder. Key words: non-alcoholic fatty liver disease, cystathionine-β-synthase, cystathionine-γ-lyase, hydrogen sulfide, homocysteine. La steatose hepatique non alcoolique (NAFLD, Non-alcoholic fatty liver disease) comprend un large spectre de maladies hepatiques diagnostiquees chez des patients sans historique d'abus d'alcool. La NAFLD croit a un rythme alarmant a travers le monde. Sa pathogenese est complexe et incompletement comprise. Le systeme constitue de la cystathionine-β-synthase (CBS) et la cystathionine-γ-lyase regule le metabolisme de l'homocysteine et de la cysteine et contribue a la biosynthese de sulfure d'hydrogene ([H.sub.2]S) endogene. Cet article de revue resume ce qui est actuellement compris du systeme CBS/CSE hepatique et, pour la premiere fois, situe ce systeme comme cible therapeutique potentielle de la NAFLD. Comme il sera discute, le systeme CBS/CSE est exprime fortement dans le foie ou il est tres actif. Sa deregulation, qui se presente sous forme de modifications des niveaux circulants d'homocysteine et/ou de [H.sub.2]S, a ete rapportee chez des patients souffrant de NAFLD et dans des comorbidites associees a la NAFLD comme l'obesite et le diabete de type 2. Des liens complexes entre le systeme CBS/CSE et un certain nombre de mediateurs moleculaires du metabolisme et du stress ont aussi emerge. Differentes dysfonctions du systeme CBS/CSE ont ete rapportees dans des modeles animaux representatifs de tout le spectre de NAFLD. On anticipe qu'une nouvelle appreciation du systeme CBS/CSE hepatique qui ameliorera notre comprehension de la pathogenese de la NAFLD emergera, et qu'elle donnera lieu a l'identification de nouvelles cibles prospectives pour controler cette maladie. [Traduit par la Redaction] Mots-cles: steatose hepatique non alcoolique, cystathionine-β-synthase, cystathionine-γ-lyase, sulfure d'hydrogene, homocysteine., Introduction Non-alcoholic fatty liver disease (NAFLD) is a broad spectrum liver disorder diagnosed in patients without a history of alcohol abuse (Chalasani et al. 2012). Hepatic steatosis or 'fatty liver', [...]

Cannabinoid receptor type-1 (CB1) is known to have a substantial impact on the regulation of energy metabolism via central and peripheral mechanisms. In this issue of the JCI, Ruiz de Azua and colleagues provide important insights into the regulation of adipocyte physiology by CB1. Mice with adipocyte-specific deletion of the CBI-encoding gene had an overall improved metabolic profile in addition to reduced body weight and total adiposity. These changes were associated with an increase in sympathetic tone of the adipose tissue and expansion of activated macrophages, both of which occurred prior to changes in body weight, lending support to a causal relationship between loss of CB1 in adipocytes and systemic metabolic changes. This work identifies adipocyte CB1s as a potential novel peripheral target for affecting systemic metabolism with diminished CNS effects., Effective obesity treatment with tolerable side effects Obesity is caused by a chronic imbalance between energy intake and expenditure. The growing incidence of obesity, especially in children and adolescents, is [...]

The global increase in the prevalence of dementia and its associated comorbidities and consequences has stimulated intensive research focused on better understanding of the basic mechanisms and the possibilities to prevent and/or treat cognitive decline or dementia. The etiology of cognitive decline and dementia is very complex and is based upon the interplay of genetic and environmental factors. A growing body of epidemiological evidence has suggested that metabolic syndrome and its components may be important in the development of cognitive decline. Furthermore, an abnormal body mass index in middle age has been considered as a predictor for the development of dementia. The Nutrition and Dementia Project (NutrDem Project) was started at the Department of Old Age Psychiatry and Psychotic Disorders with close cooperation with Department of Medical Psychology. The aim of this study is to determine the effect of dietary patterns, nutritional status, body composition (with evaluation of visceral fat) and basic regulatory mechanisms of metabolism in elderly patients on cognitive functions and the risk of cognitive impairment (mild cognitive impairment and/or dementia). European Journal of Clinical Nutrition (2014) 68, 1200-1203; doi:10.1038/ejcn.2014.171; published online 20 August 2014, INTRODUCTION The global increase in the prevalence of dementia and its associated comorbidities and consequences has stimulated intensive research focused on better understanding of the basic mechanisms and the possibilities [...]

We evaluated the effects of oral glycerol supplementation on trained rats fed a normal diet. Wistar rats were distributed among 6 groups in a completely randomized 2x3 factorial design. The animals were subjected to 6 weeks of aerobic training. In the last 4 weeks, the animals' diet was supplemented with saline, glucose, or glycerol. Data were subjected to one-way analysis of variance (ANOVA) followed by a Student-Newmann-Keuls test, with values for P < 0.05 considered statistically significant. The change in body mass was lower in the trained groups, and their food and water consumption were higher. Glycerol supplementation resulted in an increase in the levels of triacylglycerol (TAG) and total cholesterol, as well as in the area and diameter of adipocytes. When associated with training, these parameters were similar to those of other trained groups. Levels of low-density lipoprotein + very-low-density lipoprotein cholesterol decreased in the trained animals that received glycerol compared with the non-trained ones. Glycerol consumption caused a reduction in food intake and increased the villous: crypt (V:C) ratio. No changes in glycemia, high density lipoproteins, or density of adipocytes were observed. Supplementation with glycerol together with aerobic physical training promoted beneficial metabolic effects. However, in non-trained rats glycerol increased the diameter and area of adipocytes, as well as the levels of TAG and total cholesterol. Key words: glycerin, sports nutrition, physical activity, exercise, metabolism, animal model. Les auteurs ont evalue les effets d'une supplementation orale en glycerol chez des rats entraines soumis a une diete normale. Des rats Wistar ont ete repartis en six groupes dans un plan d'experience factoriel 2x3 randomise complet. Les animaux ont ete soumis a un entrainement aerobique de six semaines. Lors de quatre dernieres semaines, les animaux ont recu une supplementation en saline, en glucose ou en glycerol. Les donnees ont ete soumises a une analyse de variance (ANOVA) suivie d'un test SNK a 5 %. Le changement de poids corporel etait plus faible chez les groupes entraines et leur consommation de nourriture et d'eau etait plus elevee. La supplementation en glycerol resultait en un accroissement des niveaux de triglycerides (TG), de cholesterol total, de meme de la surface et du diametre des adipocytes. Lorsque associes a l'entrainement, ces parametres etaient similaires a ceux des autres groupes entraines. Les niveaux de LDL + VLDL-C diminuaient chez les animaux entraines qui recevaient du glycerol, comparativement aux animaux non-entraines. La consommation de glycerol produisait une reduction de la prise alimentaire et augmentait le rapport villosites : cryptes. Aucun changement de glycemie, des lipoproteines de haute densite et de la densite des adipocytes n'a ete observe. La supplementation en glycerol associee a un entrainement physique aerobique favorisait des effets metaboliques benefiques. Cependant, chez les rats non-entraines, elle accroissait le diametre et la surface des adipocytes ainsi que les niveaux de TG et de cholesterol total. [Traduit par la Redaction] Mots-cles: glycerine, nutrition sportive, activite physique, exercice, metabolisme, modele animal., Introduction The practice of physical activity has been considered one of the most efficient strategies for the control and reduction of body mass, particularly when associated with weight loss diets [...]

The climate-active gas methane is generated both by biological processes and by thermogenic decomposition of fossil organic material, which forms methane and short-chain alkanes, principally ethane, propane and butane (1,2). In addition to natural sources, environments are exposed to anthropogenic inputs of all these gases from oil and gas extraction and distribution. The gases provide carbon and/or energy for a diverse range of microorganisms that can metabolize them in both anoxic (3) and oxic zones. Aerobic methanotrophs, which can assimilate methane, have been considered to be entirely distinct from utilizers of short-chain alkanes, and studies of environments exposed to mixtures of methane and multi-carbon alkanes have assumed that disparate groups of microorganisms are responsible for the metabolism of these gases. Here we describe the mechanism by which a single bacterial strain, Methylocella silvestris, can use methane or propane as a carbon and energy source, documenting a methanotroph that can utilize a short-chain alkane as an alternative to methane. Furthermore, during growth on a mixture of these gases, efficient consumption of both gases occurred at the same time. Two soluble di-iron centre monooxygenase (SDIMO) gene clusters were identified and were found to be differentially expressed during bacterial growth on these gases, although both were required for efficient propane utilization. This report of a methanotroph expressing an additional SDIMO that seems to be uniquely involved in short-chain alkane metabolism suggests that such metabolic flexibility may be important in many environments where methane and short-chain alkanes co-occur., Most of the 500-600 Tg methane emitted into the atmosphere each year is of recent biological origin, whereas fossil-derived 'natural gas', from both anthropogenic and natural sources, contributes approximately 30% [...]

BACKGROUND/OBJECTIVES: High calcium intakes enhance fat loss under restricted energy intake. Mechanisms explaining this may involve reduced dietary fat absorption, enhanced lipid utilization and (or) reductions in appetite. This study aimed to assess the impact of 2 weeks of calcium supplementation on substrate utilization during exercise and appetite sensations at rest. SUBJECTS/METHODS: Thirteen physically active males completed two 14-d supplemental periods, in a double-blind, randomized crossover design separated by a ≥ 4-week washout period. During supplementation, a test-drink was consumed daily containing 400 and 1400 mg of calcium during control (CON) and high-calcium (CAL) periods, respectively. Cycling-based exercise tests were conducted before and after each supplemental period to determine substrate utilization rates and circulating metabolic markers (non-esterified fatty acid, glycerol, glucose and lactate concentrations) across a range of exercise intensities. Visual analog scales were completed in the fasting, rested state to determine subjective appetite sensations. RESULTS: No significant differences between supplements were observed in lipid or carbohydrate utilization rates, nor in circulating metabolic markers (both P>0.05). Maximum rates of lipid utilization were 0.47 ± 0.05 and 0.44 ± 0.05 g/min for CON and CAL, respectively, prior to supplementation and 0.44 ± 0.05 and 0.42 [+ or -] 0.05 g/min, respectively, post- supplementation (main effects of time, supplement and time x supplement interaction effect all P>0.05). Furthermore, no significant differences were detected in any subjective appetite sensations (all P>0.05). CONCLUSIONS: Two weeks of calcium supplementation does not influence substrate utilization during exercise in physically active males. European Journal of Clinical Nutrition (2014) 68, 712-718; doi:10.1038/ejcn.2014.41; published online 19 March 2014, INTRODUCTION A growing body of research implicates calcium intake in adipose regulation. Epidemiology links high-calcium intake with reduced body fat percentage, (1) and interventions demonstrate accelerated loss of adipose tissue. [...]

BACKGROUND/OBJECTIVES: To develop and crossvalidate new equations for predicting basal metabolic rate (BMR) in obese children and adolescents in relation to pubertal stages, anthropometric characteristics or body composition. SUBJECTS/METHODS: A total of 1696 obese Caucasian children and adolescents (mean body mass index z-score: 3.5 ± 0.8) participated in this study. BMR was determined by indirect calorimetry and fat-free mass (FFM) and fat mass (FM) by bioelectrical impedance analysis. Equations were derived by stepwise multiple regression analysis using a calibration cohort of 848 subjects, and the equations were crossvalidated with a Bland and Altman method in the remaining 848 subjects. RESULTS: Two new specific equations based on gender (1: males; 0: females), pubertal stages (from 1 to 5, assessed according Marshall & Tanner methods) and body weight (BW, kg), stature (m) or body composition (kg) were generated as follows: (1) BMR = (BW x 0.044) + (stature x 2.836) - (pubertal stage x 0.148) + (gender x 0.781) - 0.551 (adjusted coefficient of determination ([R.sup.2.sub.adj]) = 0.69 and root mean squared error (RMSE) = 0.954 MJ);(2) BMR = (FFM x 0.082) + (FM x 0.037) - (pubertal stage x 0.125) + (gender x 0.706) + 2.528 ([R.sup.2.sub.adj] = 0.70 and RMSE = 0.943 MJ). In the crossvalidation group, mean-predicted BMR was not significantly different from the mean-measured BMR (MBMR) for all children and adolescents, as well as for boys and girls (difference < 2 %), and the limits of agreement ([+ or -] 2 s.d.) were +1.95 and -1.98 MJ/d, (P = NS). BMR was predicted accurately (90-110% of MBMR) in 67% of subjects. CONCLUSION: The new prediction equations considering the pubertal stages allow an accurate and more appropriate (vs equations using chronological age) estimation of BMR in obese children and adolescents. European Journal of Clinical Nutrition (2014) 68, 695-699; doi:10.1038/ejcn.2014.26; published online 5 March 2014, INTRODUCTION Obesity is an increasing health problem in children and adolescents in all countries of the industrialized world. (1,2) The progressive increase in adiposity is the result of a prolonged [...]