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The housefly (Musca domestica) is a common insect species with only a few recurrent bacterial taxa in its gut microbiota, because the numerous microbial acquisition routes in its septic habitats can favor transient microbes. Here, we investigated the role of the diet on the microbiota and the developmental success of a housefly strain reared on three substrates. We used a control wheat bran-based substrate, and added clotted cream and sucrose to make a high-fat, and a high-sugar substrate, respectively. The conducted survey revealed that, in contrast to the high-fat diet, the high-sugar diet caused lower developmental success and less diverse microbiota, in which several lactobacilli were replaced with Weissella bacterial phylotypes. Cultures with sucrose as the sole carbon source confirmed that a Weissella confusa strain, isolated from larvae, could utilize sucrose more efficiently than other tested lactic acid bacteria; a result also supported by gene function prediction analysis. Enhancing the rearing substrate with Limosilactobacillus fermentum and Lactiplantibacillus plantarum strains, which were isolated from control larvae, could not only revert the negative effect of the high-sucrose diet on development, but also increase the gut bacterial diversity. In our study, we show that the microbiota shifts in response to the high-sucrose diet did not benefit the host, that showed lower developmental success. In contrast, high-sucrose favored specific components of the microbiota, that continued to be enriched even after multiple generations, outcompeting beneficial bacteria. Also, microbiome manipulation showed the potential of probiotics to rescue host performance and restore the microbiome., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Polyhydroxybutyrate (PHB) is a bio-based, biodegradable and biocompatible plastic that has the potential to replace petroleum-based plastics. Lignocellulosic biomass is a promising feedstock for industrial fermentation to produce bioproducts such as polyhydroxybutyrate (PHB). However, the pretreatment processes of lignocellulosic biomass lead to the generation of toxic byproducts, such as furfural, 5-HMF, vanillin, and acetate, which affect microbial growth and productivity. In this study, to reduce furfural toxicity during PHB production from lignocellulosic hydrolysates, we genetically engineered Cupriavidus necator NCIMB 11599, by inserting the nicotine amide salvage pathway genes pncB and nadE to increase the NAD(P)H pool. We found that the expression of pncB was the most effective in improving tolerance to inhibitors, cell growth, PHB production and sugar consumption rate. In addition, the engineered strain harboring pncB showed higher PHB production using lignocellulosic hydrolysates than the wild-type strain. Therefore, the application of NAD salvage pathway genes improves the tolerance of Cupriavidus necator to lignocellulosic-derived inhibitors and should be used to optimize PHB production., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study examined associations between BMI and dietary sugar intake with sucrose-induced fibroblast growth factor 21 (FGF21) and whether circulating FGF21 is associated with brain signaling following sucrose ingestion in humans., Methods: A total of 68 adults (29 male; mean [SD), age 23.2 [3.8] years; BMI 27.1 [4.9] kg/m 2 ) attended visits after a 12-hour fast. Plasma FGF21 was measured at baseline and at 15, 30, and 120 minutes after sucrose ingestion (75 g in 300 mL of water). Brain cerebral blood flow responses to sucrose were measured using arterial spin labeling magnetic resonance imaging., Results: Higher circulating FGF21 levels were associated with reduced blood flow in the striatum in response to sucrose (β = -7.63, p = 0.03). This association was greatest among persons with healthy weight (β = -15.70, p = 0.007) and was attenuated in people with overweight (β = -4.00, p = 0.63) and obesity (β = -12.45, p = 0.13). BMI was positively associated with FGF21 levels in response to sucrose (β = 0.53, p = 0.02). High versus low dietary sugar intake was associated with greater FGF21 responses to acute sucrose ingestion in individuals with healthy weight (β = 8.51, p = 0.04) but not in individuals with overweight or obesity (p > 0.05)., Conclusions: These correlative findings support evidence in animals showing that FGF21 acts on the brain to regulate sugar consumption through a negative feedback loop., (© 2022 The Obesity Society.)

This systematic review aimed to reveal the differential brain processing of sugars and sweeteners in humans. Functional magnetic resonance imaging studies published up to 2019 were retrieved from two databases and were included into the review if they evaluated the effects of both sugars and sweeteners on the subjects' brain responses, during tasting and right after ingestion. Twenty studies fulfilled the inclusion criteria. The number of participants per study ranged from 5 to 42, with a total number of study participants at 396. Seven studies recruited both males and females, 7 were all-female and 6 were all-male. There was no consistent pattern showing that sugar or sweeteners elicited larger brain responses. Commonly involved brain regions were insula/operculum, cingulate and striatum, brainstem, hypothalamus and the ventral tegmental area. Future studies, therefore, should recruit a larger sample size, adopt a standardized fasting duration (preferably 12 h overnight, which is the most common practice and brain responses are larger in the state of hunger), and reported results with familywise-error rate (FWE)-corrected statistics. Every study should report the differential brain activation between sugar and non-nutritive sweetener conditions regardless of the complexity of their experiment design. These measures would enable a meta-analysis, pooling data across studies in a meaningful manner.

Alterations of transition metal levels have been associated with obesity, hepatic steatosis, and metabolic syndrome in humans. Studies in animals indicate an association between dietary sugars and copper metabolism. Our group has conducted a study in which young adults consumed beverages sweetened with glucose, fructose, high fructose corn syrup (HFCS), or aspartame for two weeks and has reported that consumption of both fructose- and HFCS-sweetened beverages increased cardiovascular disease risk factors. Baseline and intervention serum samples from 107 participants of this study were measured for copper metabolism (copper, ceruloplasmin ferroxidase activity, ceruloplasmin protein), zinc levels, and iron metabolism (iron, ferritin, and transferrin) parameters. Fructose and/or glucose consumption were associated with decreased ceruloplasmin ferroxidase activity and serum copper and zinc concentrations. Ceruloplasmin protein levels did not change in response to intervention. The changes in copper concentrations were correlated with zinc, but not with iron. The decreases in copper, ceruloplasmin ferroxidase activity, ferritin, and transferrin were inversely associated with the increases in metabolic risk factors associated with sugar consumption, specifically, apolipoprotein CIII, triglycerides, or post-meal glucose, insulin, and lactate responses. These findings are the first evidence that consumption of sugar-sweetened beverages can alter clinical parameters of transition metal metabolism in healthy subjects.

Sugar administration prior acute psychosocial stress exposure was shown to enhance subsequent salivary cortisol responses. However, this finding is based on studies that have administered high doses of glucose to male subjects after long fasting periods. Therefore, in the present study, we investigated the effect of different sugar-containing drinks on acute cortisol stress responses under experimental conditions that are commonplace in stress research and our sample included females and males. Our primary aim was to derive feasible recommendations for a standardized sugar administration in future studies. Of the 103 healthy young participants (49 females, 54 males), 72 were confronted with the Trier Social Stress Test after being randomly assigned to one of three sugar conditions (200 ml of grape juice, a 75 g glucose or a 75 g maltodextrin drink); 31 subjects served as control sample and were exposed to the TSST without sugar administration. Cortisol stress responses were significantly enhanced in the grape juice as well as the glucose group as compared to the control group. Post hoc analysis revealed that this effect seemed to be more pronounced in males than in females. We did not find a significant effect of maltodextrin. Cortisol responder rates in all three experimental groups were higher than in the control group. Our results suggest that, at least in males, the administration of 200 ml of grape juice is sufficient to facilitate HPA axis reactivity and to minimize confounding effects due to interindividual differences in energy availability while being exposed to a laboratory stress paradigm. The unexpected gender-specific effect is of potential relevance and should be scrutinized in future studies., Competing Interests: Declaration of Competing Interest All authors report no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: High dietary fat and sugar promote cardiac hypertrophy independently from an increase in blood pressure. The respective contribution that each macronutrient exerts on cardiac growth signaling pathways remains unclear., Objective: The goal of this study was to investigate the mechanisms by which high amounts of dietary fat and sugar affect cardiac growth regulatory pathways., Methods: Male C57BL/6 mice (9 wk old; n = 20/group) were fed a standard rodent diet (STD; kcal% protein-fat-carbohydrate, 29-17-54), a high-fat diet (HFD; 20-60-20), a high-fat and high-sugar Western diet (WD; 20-45-35), a high-sugar diet with mixed carbohydrates (HCD; 20-10-70), or a high-sucrose diet (HSD; 20-10-70). Body composition was assessed weekly by EchoMRI. Whole-body glucose utilization was assessed with an intraperitoneal glucose tolerance test. After 6 wk on diets, mice were treated with saline or 20 mg/kg isoproterenol (ISO), and the activity of cardiac growth regulatory pathways was analyzed by immunoblotting. Data were analyzed by ANOVA with data from the STD group included for references only., Results: Compared with HCD and HSD, WD and HFD increased body fat mass 2.7- to 3.8-fold (P < 0.001), induced glucose intolerance (P < 0.001), and increased insulin concentrations >1.5-fold (P < 0.05), thereby enhancing basal and ISO-stimulated AKT phosphorylation at both threonine 308 and serine 473 residues (+25-63%; P < 0.05). Compared with HFD, the high-sugar diets potentiated ISO-mediated stimulation of the glucose-sensitive kinases PYK2 (>47%; P < 0.05 for HCD and HSD) and ERK (>34%; P < 0.05 for WD, HCD, and HSD), thereby leading to increased phosphorylation of protein synthesis regulator S6K1 at threonine 389 residue (>64%; P < 0.05 for WD, HCD, and HSD)., Conclusions: Dietary fat and sugar affect cardiac growth signaling pathways in C57BL/6 mice through distinct and additive mechanisms. The findings may provide new insights into the role of overnutrition in pathological cardiac remodeling., (Copyright © The Author(s) 2020.)

Consumption of fructose has risen markedly in recent decades owing to the use of sucrose and high-fructose corn syrup in beverages and processed foods 1 , and this has contributed to increasing rates of obesity and non-alcoholic fatty liver disease 2-4 . Fructose intake triggers de novo lipogenesis in the liver 4-6 , in which carbon precursors of acetyl-CoA are converted into fatty acids. The ATP citrate lyase (ACLY) enzyme cleaves cytosolic citrate to generate acetyl-CoA, and is upregulated after consumption of carbohydrates 7 . Clinical trials are currently pursuing the inhibition of ACLY as a treatment for metabolic diseases 8 . However, the route from dietary fructose to hepatic acetyl-CoA and lipids remains unknown. Here, using in vivo isotope tracing, we show that liver-specific deletion of Acly in mice is unable to suppress fructose-induced lipogenesis. Dietary fructose is converted to acetate by the gut microbiota 9 , and this supplies lipogenic acetyl-CoA independently of ACLY 10 . Depletion of the microbiota or silencing of hepatic ACSS2, which generates acetyl-CoA from acetate, potently suppresses the conversion of bolus fructose into hepatic acetyl-CoA and fatty acids. When fructose is consumed more gradually to facilitate its absorption in the small intestine, both citrate cleavage in hepatocytes and microorganism-derived acetate contribute to lipogenesis. By contrast, the lipogenic transcriptional program is activated in response to fructose in a manner that is independent of acetyl-CoA metabolism. These data reveal a two-pronged mechanism that regulates hepatic lipogenesis, in which fructolysis within hepatocytes provides a signal to promote the expression of lipogenic genes, and the generation of microbial acetate feeds lipogenic pools of acetyl-CoA.

Strong evidence supports a major role for heterodimers of the type 1 taste receptor (T1R) family in the taste transduction of sugars (T1R2+T1R3) and amino acids (T1R1+T1R3), but there are also neural and behavioral data supporting T1R-independent mechanisms. Most neural evidence for alternate mechanisms comes from whole nerve recordings in mice with deletion of a single T1R family member, limiting conclusions about the functional significance and T1R independence of the remaining responses. To clarify these issues, we recorded single-unit taste responses from the nucleus of the solitary tract in T1R double-knockout (double-KO) mice lacking functional T1R1+T1R3 [KO1+3] or T1R2+T1R3 [KO2+3] receptors and their wild-type background strains [WT; C57BL/6J (B6), 129X1/SvJ (S129)]. In both double-KO strains, responses to sugars and a moderate concentration of an monosodium glutamate + amiloride + inosine 5'-monophosphate cocktail (0.1 M, i.e., umami) were profoundly depressed, whereas a panel of 0.6 M amino acids were mostly unaffected. Strikingly, in contrast to WT mice, no double-KO neurons responded selectively to sugars and umami, precluding segregation of this group of stimuli from those representing other taste qualities in a multidimensional scaling analysis. Nevertheless, residual sugar responses, mainly elicited by monosaccharides, persisted as small "sideband" responses in double-KOs. Thus other receptors may convey limited information about sugars to the central nervous system, but T1Rs appear critical for coding the distinct perceptual features of sugar and umami stimuli. The persistence of amino acid responses supports previous proposals of alternate receptors, but because these stimuli affected multiple neuron types, further investigations are necessary. NEW & NOTEWORTHY The type 1 taste receptor (T1R) family is crucial for transducing sugars and amino acids, but there is evidence for T1R-independent mechanisms. In this study, single-unit recordings from the nucleus of the solitary tract in T1R double-knockout mice lacking T1R1+T1R3 or T1R2+T1R3 receptors revealed greatly reduced umami synergism and sugar responses. Nevertheless, residual sugar responses persisted, mainly elicited by monosaccharides and evident as "sidebands" in neurons activated more vigorously by other qualities.

Aims: Our aim was to evaluate the acute effect of eating sweet snacks at different times of day on glycaemic parameters in young women without diabetes., Methods: In this randomized controlled three-treatment crossover study, 17 women [(means ± SD) age: 21.2 ± 0.8 years, BMI: 20.7 ± 2.5 kg/m2, HbA 1c : 36 ± 2 mmol/mol (5.1 ± 0.2%)] wore flash (continuous) glucose monitoring systems for 7 days. Each participant consumed identical test meals on days 4, 5 and 6, but consumed sweet snacks (baked cake: 498 kcal; 53.6 g of carbohydrate, 8.0 g of protein, 28.0 g of fat) at 12:30 (post-lunch), 15:30 (mid-afternoon) and 19:30 (post-dinner), respectively, on each of those days. Daily glycaemic parameters on those 3 days of snacking at different times of day were compared within-participant., Results: The mean amplitude of glycaemic excursions (3.54 ± 0.32 vs. 2.73 ± 0.20 mmol/L; P < 0.05), standard deviation of glucose (1.20 ± 0.11 vs. 0.92 ± 0.07 mmol/L; P < 0.05), incremental area under the curve (IAUC) for glucose at 12:00-07:00 (986 ± 89 vs. 716 ± 88 mmol/L × min; P < 0.05) and IAUC at 07:00-10:00 the next day (141 ± 17 vs. 104 ± 12 mmol/L × min; P < 0.05) when the snack was eaten post-dinner were all significantly higher than with mid-afternoon snacking., Conclusion: Eating sweet snacks post-dinner should be avoided because it worsens glucose excursions as well as postprandial glucose levels after both dinner and the following day's breakfast in young healthy (non-diabetic) women., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Differential expression of 30,003 genes was studied in the liver of female Wistar rats fed with isocaloric diets with the excess of fat, fructose, or cholesterol, or their combinations for 62 days using the method of whole-transcriptome profiling on a microchip. Relative mRNA expression levels of the Asah2, Crot, Crtc2, Fmo3, GSTA2, LOC1009122026, LOC102551184, NpY, NqO1, Prom1, Retsat, RGD1305464, Tmem104, and Whsc1 genes were also determined by RT-qPCR. All the tested diets affected differently the key metabolic pathways (KEGGs). Significant changes in the expression of steroid metabolism gene were observed in the liver of animals fed with the tested diets (except the high-fat high fructose diet). Both high-fat and high-fructose diets caused a significant decrease in the expression of squalene synthase (FDFT1 gene) responsible for the initial stage of cholesterol synthesis. On the contrary, in animals fed with the high-cholesterol diet (0.5% cholesterol), expression of the FDFT1 gene did not differ from the control group; however, these animals were characterized by changes in the expression of glucose and glycogen synthesis genes, which could lead to the suppression of glycogen synthesis and gluconeogenesis. At the same time, this group demonstrated different liver tissue morphology in comparison with the animals fed with the high-fructose high-fat diet, manifested as the presence of lipid vacuoles of a smaller size in hepatocytes. The high-fructose and high-fructose high-fat diets affected the metabolic pathways associated with intracellular protein catabolism (endocytosis, phagocytosis, proteasomal degradation, protein processing in the endoplasmic reticulum), tight junctions and intercellular contacts, adhesion molecules, and intracellular RNA transport. Rats fed with the high-fructose high-fat or high-cholesterol diets demonstrated consistent changes in the expression of the Crot, Prom1, and RGD1305464 genes, which reflected a coordinated shift in the regulation of lipid and carbohydrate metabolisms.

Dendritic cells (DCs) are critical antigen-presenting cells which are the initiators and regulators of the immune response. Numerous studies support the idea that dietary sugars influence DC functions. Increased consumption of fructose has been thought to be the leading cause of metabolic disorders. Although evidence supports their association with immune dysfunction, the specific mechanisms are not well understood. Fructose is one of the main dietary sugars in our diet. Therefore, here we compared the effect of fructose and glucose on the functions of human DCs. High levels of D-fructose compared to D-glucose led to activation of DCs in vitro by promoting interleukin (IL)-6 and IL-1β production. Moreover, fructose exposed DCs also induced interferon (IFN)-γ secretion from T cells. Proinflammatory response of DCs in high fructose environment was found to be independent of the major known metabolic regulators or glycolytic control. Instead, DC activation on acute exposure to fructose was via activation of receptor for advanced glycation end product (RAGE) in response to increased accumulation of advanced glycation end products (AGE). However, chronic exposure of DCs to high fructose environment induced a shift towards glycolysis compared to glucose cultured DCs. Further investigations revealed that the AGEs formed by fructose induced increased levels of inflammatory cytokines in DCs compared to AGEs from glucose. In summary, understanding the link between metabolic changes and fructose-induced DC activation compared to glucose has broad implications for immune dysfunction associated with metabolic disorders., (© 2019 British Society for Immunology.)

Recent studies find that sugar tastes less intense to humans with obesity, but whether this sensory change is a cause or a consequence of obesity is unclear. To tackle this question, we study the effects of a high sugar diet on sweet taste sensation and feeding behavior in Drosophila melanogaster. On this diet, fruit flies have lower taste responses to sweet stimuli, overconsume food, and develop obesity. Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons. Correcting taste deficits by manipulating the excitability of the sweet gustatory neurons or the levels of OGT protected animals from diet-induced obesity. Our work demonstrates that the reshaping of sweet taste sensation by excess dietary sugar drives obesity and highlights the role of glucose metabolism in neural activity and behavior., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

It is difficult to know if the cause for obesity is the type of sweetener, high fat (HF) content, or the combination of sweetener and fat. The purpose of the present work was to study different types of sweeteners; in particular, steviol glycosides (SG), glucose, fructose, sucrose, brown sugar, honey, SG + sucrose (SV), and sucralose on the functionality of the adipocyte. Male Wistar rats were fed for four months with different sweeteners or sweetener with HF added. Taste receptors T1R2 and T1R3 were differentially expressed in the tongue and intestine by sweeteners and HF. The combination of fat and sweetener showed an additive effect on circulating levels of GIP and GLP-1 except for honey, SG, and brown sugar. In adipose tissue, sucrose and sucralose stimulated TLR4, and c-Jun N-terminal (JNK). The combination of HF with sweeteners increased NFκB, with the exception of SG and honey. Honey kept the insulin signaling pathway active and the smallest adipocytes in white (WAT) and brown (BAT) adipose tissue and the highest expression of adiponectin, PPARγ, and UCP-1 in BAT. The addition of HF reduced mitochondrial branched-chain amino transferase (BCAT2) branched-chain keto acid dehydrogenase E1 (BCKDH) and increased branched chain amino acids (BCAA) levels by sucrose and sucralose. Our data suggests that the consumption of particular honey maintained functional adipocytes despite the consumption of a HF diet.

Excessive maternal high-fructose diet (HFD) during pregnancy and lactation has been reported to cause metabolic disorders in the offspring. Whether the infant's brain metabolism is disturbed by maternal HFD is largely unknown. Brain energy metabolism is elevated dramatically during fetal and postnatal development, whereby maternal nutrition is a key factor that determines cellular metabolism. Astrocytes, a nonneuronal cell type in the brain, are considered to support the high-energy demands of neurons by supplying lactate. In this study, the effects of maternal HFD on astrocytic glucose metabolism were investigated using hippocampal primary cultures of female infants. We found that glycolytic capacity and mitochondrial respiration and electron transport chain were suppressed by maternal HFD. Mitochondrial DNA copy number and mitochondrial transcription factor A expression were suppressed by maternal HFD. Western blots and immunofluorescent images further indicated that the glucose transporter 1 was downregulated whereas the insulin receptor-α, phospho-insulin receptor substrate-1 (Y612) and the p85 subunit of phosphatidylinositide 3-kinase were upregulated in the HFD group. Pioglitazone, which is known to increase astrocytic glucose metabolism, effectively reversed the suppressed glycolysis, and lactate release was restored. Moreover, pioglitazone also normalized oxidative phosphorylation with an increase of cytosolic ATP. Together, these results suggest that maternal HFD impairs astrocytic energy metabolic pathways that were reversed by pioglitazone.

Objective: The brain is essential in regulating intake of food and beverages by balancing energy homeostasis, which is regulated by the hypothalamus, with reward perception, which is regulated by the ventral tegmental area (VTA). The aim of this study was to investigate the effects of ingestion of glucose, fructose, sucrose, and sucralose (a non-caloric artificial sweetener) on the magnitude and trajectory of the hypothalamic and the VTA blood oxygen level-dependent (BOLD) responses., Method: In five visits, 16 healthy men between 18 to 25 y of age with a body mass index between 20 and 23 kg/m 2 drank five interventions in a randomized order while a functional magnetic resonance imaging scan was taken. The interventions consisted of 50 g of glucose, fructose, or sucrose, or 0.33 g of sucralose dissolved in 300 mL tap water. The control condition consisted of 300 mL of plain tap water. BOLD signals were determined in the hypothalamus and the VTA within a manually drawn region of interest. Differences in changes in BOLD signal between stimuli were analyzed using mixed models., Results: Compared with the control condition, a decrease in BOLD signal in the hypothalamus was found after ingestion of glucose (P = 0.0003), and a lesser but delayed BOLD response was found after ingestion of sucrose (P = 0.006) and fructose (P = 0.003). Sucralose led to a smaller and transient response from the hypothalamus (P = 0.026). In the VTA, sucralose led to a very similar response to the water control condition, leading to an increase in VTA BOLD activity that continued over the measured time period. The natural sugars appeared to only lead to a transient increase in VTA activity., Conclusions: Glucose induces a deactivation in the hypothalamus immediately after ingestion and continued over the next 12 min, which is correlated with satiety signaling by the brain. Fructose and sucrose are both associated with a delayed and lesser response from the hypothalamus, likely because the sugars first have to be metabolized by the body. Sucralose leads to the smallest and most transient decrease in BOLD in the hypothalamus and leads to a similar response as plain water in the VTA, which indicates that sucralose might not have a similar satiating effect on the brain as the natural sugars., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The composition of the gut microbiota is largely determined by environmental factors including the host diet. Dietary components are believed to influence the composition of the gut microbiota by serving as nutrients to a subset of microbes, thereby favoring their expansion. However, we now report that dietary fructose and glucose, which are prevalent in the Western diet, specifically silence a protein that is necessary for gut colonization, but not for utilization of these sugars, by the human gut commensal Bacteroides thetaiotaomicron Silencing by fructose and glucose requires the 5' leader region of the mRNA specifying the protein, designated Roc for regulator of colonization. Incorporation of the roc leader mRNA in front of a heterologous gene was sufficient for fructose and glucose to turn off expression of the corresponding protein. An engineered strain refractory to Roc silencing by these sugars outcompeted wild-type B. thetaiotaomicron in mice fed a diet rich in glucose and sucrose (a disaccharide composed of glucose and fructose), but not in mice fed a complex polysaccharide-rich diet. Our findings underscore a role for dietary sugars that escape absorption by the host intestine and reach the microbiota: regulation of gut colonization by beneficial microbes independently of supplying nutrients to the microbiota., Competing Interests: The authors declare no conflict of interest.

Background: Consumption of added sugars (AS) and sugar-sweetened beverages (SSB) may adversely affect adolescents' weight and cardiovascular disease risk. Reliance on self-reported dietary assessment methods is a common research limitation, which could be overcome by dietary intake biomarkers., Aim: The investigation was a proof-of-concept study to evaluate the proposed carbon isotope ratio (δ 13 C) biomarker of AS intake in adolescents, using a controlled feeding design., Methods: Participants ( n = 33, age 15.3 years, 53% female) underwent two seven-day controlled feeding periods in a randomly assigned order. Diets were matched in composition except for AS content (5% or 25% of total energy). Fasting fingerstick blood samples were collected daily during each diet period., Results: Fingerstick δ 13 C values changed from day 1 to 8 by -0.05 ± 0.071‰ on 5% AS, and +0.03 ± 0.083‰ on 25% AS ( p ≤ 0.001). Reliability was demonstrated between day 7 and 8 δ 13 C values on the 5% (ICC = 0.996 , p ≤ 0.001) and 25% (ICC = 0.997, p ≤ 0.001) AS diets., Conclusions: Larger scale investigations are warranted to determine if this technique could be applied to population-level research in order to help assess the effectiveness of interventions aimed at reducing the consumption of AS or SSB intake.

Increased intestinal barrier permeability has been correlated with aging and disease, including type 2 diabetes, Crohn's disease, celiac disease, multiple sclerosis and irritable bowel syndrome. The prevalence of these ailments has risen together with an increase in industrial food processing and food additive consumption. Additives, including sugar, metal oxide nanoparticles, surfactants and sodium chloride, have all been suggested to increase intestinal permeability. We used two complementary model systems to examine the effects of food additives on gut barrier function: a Drosophila in vivo model and an in vitro human cell co-culture model. Of the additives tested, intestinal permeability was increased most dramatically by high sugar. High sugar also increased feeding but reduced gut and overall animal size. We also examined how food additives affected the activity of a gut mucosal defense factor, intestinal alkaline phosphatase (IAP), which fluctuates with bacterial load and affects intestinal permeability. We found that high sugar reduced IAP activity in both models. Artificial manipulation of the microbiome influenced gut permeability in both models, revealing a complex relationship between the two. This study extends previous work in flies and humans showing that diet can play a role in the health of the gut barrier. Moreover, simple models can be used to study mechanisms underlying the effects of diet on gut permeability and function.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

It has been widely described that chronic intake of fructose causes metabolic alterations which can be associated with brain function impairment. In this study, we evaluated the effects of fructose intake on the sleep⁻wake cycle, locomotion, and neurochemical parameters in Wistar rats. The experimental group was fed with 10% fructose in drinking water for five weeks. After treatment, metabolic indicators were quantified in blood. Electroencephalographic recordings were used to evaluate the sleep architecture and the spectral power of frequency bands. Likewise, the locomotor activity and the concentrations of orexin A and monoamines were estimated. Our results show that fructose diet significantly increased the blood levels of glucose, cholesterol, and triglycerides. Fructose modified the sleep⁻wake cycle of rats, increasing the waking duration and conversely decreasing the non-rapid eye movement sleep. Furthermore, these effects were accompanied by increases of the spectral power at different frequency bands. Chronic consumption of fructose caused a slight increase in the locomotor activity as well as an increase of orexin A and dopamine levels in the hypothalamus and brainstem. Specifically, immunoreactivity for orexin A was increased in the ventral tegmental area after the intake of fructose. Our study suggests that fructose induces metabolic changes and stimulates the activity of orexinergic and dopaminergic neurons, which may be responsible for alterations of the sleep⁻wake cycle.

Palatinose is a sucrose analog with a slower digestion rate than that of sucrose. For this reason, palatinose shows better effects on hepatic lipogenesis and cholesterol homeostasis compared with sucrose. We hypothesized that supplementation with palatinose instead of sucrose improves postprandial hyperglycemia and hyperinsulinemia in mice. Herein, we compared the digestion rates in vitro and observed physiological changes in vivo between sucrose- and palatinose-containing diets given to mice. Palatinose was hydrolyzed only by enzymes of the small intestine and was digested more slowly compared with sucrose in vitro. In mice, a diet containing palatinose resulted in significantly lower body weight gain and food efficiency rate values than those given a diet with sucrose. In this study, changes in serum biochemistry; hepatic fatty acid synthesis; cholesterol homeostasis; glucogenic, proinflammatory cytokines; and oxidative stress-related genes and proteins in the palatinose- and sucrose-fed mice were measured. Compared with the mice fed the sucrose diet, the palatinose diet resulted in lower serum glucose, insulin, and total cholesterol levels, as well as lower expression of several lipogenesis-related genes and proteins. Histological analysis of hepatic cells of palatinose-fed mice showed normal morphology. In conclusion, palatinose intake results in lower hepatic lipogenesis and better cholesterol homeostasis than the effects from sucrose., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Research has shown that carbohydrate consumption can increase body temperature at rest and, in some cases, during exercise. Most exercise studies, however, haven't matched exercise intensity between carbohydrate and placebo conditions. The purpose of this randomized, double-blind, placebo-controlled trial was to examine whether pre-exercise carbohydrate consumption independently accelerates the usual temperature rise with intense exercise. Twenty-eight runners self-reported 5-km performance (16-23 min) and were randomized, using a matched-pairs design, to 750 ml water containing 100 g sucrose or 0.8 g aspartame. Beverages were consumed 60 min before running at 93% of maximum 5-km speed in temperate conditions. Gastrointestinal temperature, Thermal Sensation Scale (TSS) and Feeling Scale (FS) were recorded before ingestion, every 10 min during 60 min of rest, and every 1-km during the 5-km run. Rating of Perceived Exertion was recorded every 1-km. Independent samples t-tests and two-way mixed ANOVAs with repeated measures assessed whether there were baseline differences or treatment effects. Gastrointestinal temperature didn't differ between carbohydrate (38.7 ± 0.4 °C) and placebo (38.6 ± 0.4 °C) by the end of the 5-km (p = 0.49). No group x time interactions or main group effects were found, except for a modest interaction for TSS (F = 2.1, p = 0.02, partial η 2 = 0.075). Time effects were found for all outcomes, with temperature, TSS, and RPE increasing, and FS decreasing, during the run. Ingesting 100 g of sucrose prior to intense running lasting < 25 min didn't influence gastrointestinal temperature and therefore doesn't likely impact on the risk of heat illness., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose of Review: The current review summarizes and discusses current research on differences elicited between sugars and nonnutritive sweeteners via sugar-sensing pathways., Recent Findings: Sugars, sweeteners, and sweetening agents are all perceived as sweet tasting because of their ability to bind to the type 1 taste receptor family of sweet taste receptors in the oral cavity. The ability of a wide variety of chemical ligands to activate the sweet taste receptor highlights the importance of sweet-tasting foods during human evolution. The sweet taste receptor has been located in the gut, and differences between oral and gut sugar-sensing pathways are discussed., Summary: Differences in the sweetness transduction cascade, and neuronal signalling may result in incretin hormone release upon activation of the sweet taste receptor from some sweeteners, but not others.

Hepatic autophagy has been shown to be regulated by acute exercise and exercise training. Moreover, high-fat diet-induced steatosis has been reported to be associated with impaired hepatic autophagy. In addition, autophagy has been shown to be regulated by acute exercise and exercise training in a PGC-1α dependent manner in skeletal muscle. The aim of this study was to test the hypotheses that high-fat high-fructose (HFF) diet changes hepatic autophagy and mitophagy, that exercise training can restore this through a PGC-1α-mediated mechanism, and that acute exercise regulates autophagy and mitophagy in the liver. Liver samples were obtained from liver-specific PGC-1α KO mice and their littermate Lox/Lox mice fed a HFF diet or a control diet for 13 weeks. The HFF mice were either exercise trained (ExT) on a treadmill the final 5 weeks or remained sedentary (UT). In addition, half of each group performed at the end of the intervention an acute 1 h exercise bout. HFF resulted in increased hepatic BNIP3 dimer and Parkin protein, while exercise training increased BNIP3 total protein without affecting the elevated BNIP3 dimer protein. In addition, exercise training reversed a HFF-induced increase in hepatic LC3II/LC3I protein ratio, as well as a decreased PGC-1α mRNA level. Acute exercise increased hepatic PGC-1α mRNA in HFF UT mice only. In conclusion, this indicates that exercise training in part reverses a HFF-induced increase in hepatic autophagy and capacity for mitophagy in a PGC-1α-independent manner. Moreover, HFF may blunt acute exercise-induced regulation of hepatic autophagy., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Insulin resistance (IR) and impaired glucose tolerance (IGT) are the first manifestations of diet-induced metabolic alterations leading to Type 2 diabetes, while hypertension is the deadliest risk factor of cardiovascular disease. The roles of dietary fat and fructose in the development of IR, IGT, and hypertension are controversial. We tested the long-term effects of an excess of fat or sucrose (fructose/glucose) on healthy male Wistar-Kyoto (WKY) rats. Fat affects IR and IGT earlier than fructose through low-grade systemic inflammation evidenced by liver inflammatory infiltration, increased levels of plasma IL-6, PGE 2 , and reduced levels of protective short-chain fatty acids without triggering hypertension. Increased populations of gut Enterobacteriales and Escherichia coli may contribute to systemic inflammation through the generation of lipopolysaccharides. Unlike fat, fructose induces increased levels of diacylglycerols (lipid mediators of IR) in the liver, urine F 2 -isoprostanes (markers of systemic oxidative stress), and uric acid, and triggers hypertension. Elevated populations of Enterobacteriales and E. coli were only detected in rats given an excess of fructose at the end of the study. Dietary fat and fructose trigger IR and IGT in clearly differentiated ways in WKY rats: early low-grade inflammation and late direct lipid toxicity, respectively; gut microbiota plays a role mainly in fat-induced IR, and hypertension is independent of inflammation-mediated IR. The results provide evidence that suggests that the combination of fat and sugar is potentially more harmful than fat or sugar alone when taken in excess.

Purpose of Review: There is increasing concern that dietary fructose may contribute to the development of noncommunicable diseases. This review identifies major new findings related to fructose's physiological or adverse effects., Recent Findings: Fructose is mainly processed in splanchnic organs (gut, liver, kidneys) to glucose, lactate, and fatty acids, which can then be oxidized in extrasplanchnic organs and tissues. There is growing evidence that splanchnic lactate production, linked to extrasplanchnic lactate metabolism, represents a major fructose disposal pathway during and after exercise. Chronic excess fructose intake can be directly responsible for an increase in intrahepatic fat concentration and for the development of hepatic, but not muscle insulin resistance. Although it has long been thought that fructose was exclusively metabolized in splanchnic organs, several recent reports provide indirect that some fructose may also be metabolized in extrasplanchnic cells, such as adipocytes, muscle, or brain cells; the quantity of fructose directly metabolized in extrasplanchnic cells, and its physiological consequences, remain however unknown. There is also growing evidence that endogenous fructose production from glucose occurs in humans and may have important physiological functions, but may also be associated with adverse health effects., Summary: Fructose is a physiological nutrient which, when consumed in excess, may have adverse metabolic effects, mainly in the liver (hepatic insulin resistance and fat storage). There is also concern that exogenous or endogenously produced fructose may be directly metabolized in extrasplanchnic cells in which it may exert adverse metabolic effects.

Sugar-containing beverages like orange juice can be a risk factor for obesity and type 2 diabetes although the underlying mechanisms are less clear. We aimed to investigate if intake of orange juice with or in-between meals differently affects energy balance or metabolic risk. Twenty-six healthy adults (24.7 ± 3.2 y; BMI 23.2 ± 3.2 kg/m 2 ) participated in a 4-week cross-over intervention and consumed orange juice (20% of energy requirement) either together with 3 meals/d (WM) or in-between 3 meals/d (BM) at ad libitum energy intake. Basal and postprandial insulin sensitivity (primary outcome), daylong glycaemia, glucose variability and insulin secretion were assessed. Body fat mass was measured by air-displacement plethysmography. After BM-intervention, fat mass increased (+1.0 ± 1.8 kg; p < 0.05) and postprandial insulin sensitivity tended to decrease (ΔMatsuda ISI : -0.89 ± 2.3; p = 0.06). By contrast, after WM-intervention fat mass and gamma-glutamyl transferase (GGT) decreased (-0.30 ± 0.65 kg; -2.50 ± 3.94; both p < 0.05), whereas glucose variability was higher (ΔMAGE: +0.45 ± 0.59, p < 0.05). Daylong glycaemia, insulin secretion, changes in basal insulin sensitivity, and triglycerides did not differ between WM- and BM-interventions (all p > 0.05). In young healthy adults, a conventional 3-meal structure with orange juice consumed together with meals had a favorable impact on energy balance, whereas juice consumption in-between meals may contribute to a gain in body fat and adverse metabolic effects.

Cardiovascular diseases are still the primary cause of mortality worldwide, with high blood pressure and type 2 diabetes as major promoters. Over the past 3 decades, almost in parallel with the rise in cardiovascular disease incidence, the consumption of sugar-sweetened beverages (SSBs) has increased. In this context, SSBs are potential contributors to weight gain and increase the risk for elevations in blood pressure, type 2 diabetes, coronary heart disease, and stroke. Nevertheless, the mechanisms underlying the cardiovascular and metabolic responses to SSBs, in particular on blood pressure, are poorly understood. We discuss and propose potential mechanisms underlying differential effects of sugars on postprandial blood pressure regulation; provide evidence for additional molecular contributors, i.e., fibroblast growth factor 21, towards sugar-induced cardiovascular responses; and discuss potential cardiovascular neutral sugars. Furthermore, we explore whether pre-existing glucose intolerance in humans exacerbates the cardiovascular responses to SSBs, thus potentially aggravating the cardiovascular risk in already-susceptible individuals.

In recent years there has been increasing interest in studying cognitive effects associated with sugar consumption. Neuro-cognitive research has confirmed that glucose, as a main energy substrate for the brain, can momentarily benefit cognitive performances, particularly for memory functioning. However, there is still limited understanding of relative effects of other common sugars (e.g., fructose and sucrose) on cognitive performance. The present study tested in 49 people the effects of three common dietary sugars against a placebo sweetener (i.e., sucralose), on performance of three well-studied cognitive tasks - simple response time, arithmetic, and Stroop interference, all of which are suggested to rely on the prefrontal lobe. A double-blind, placebo-controlled, cross-over experimental design was used. Results revealed that ingestion of glucose and sucrose led to poorer performances on the assessed tasks as opposed to fructose and the placebo (p<0.05); these effects were particularly pronounced under the fasting condition in comparison to the non-fasting condition (p<0.001). Overall, these results indicate that cognitive effects of sugar are unlikely to be mediated by the perception of sweetness. Rather, the effects are mediated by glucose. Further research should systematically assess effects of dietary sugars on other cognitive domains, such as memory, to give further insights on general cognitive effects of sugar consumption., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Clostridium difficile disease has recently increased to become a dominant nosocomial pathogen in North America and Europe, although little is known about what has driven this emergence. Here we show that two epidemic ribotypes (RT027 and RT078) have acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose. RT027 strains contain a single point mutation in the trehalose repressor that increases the sensitivity of this ribotype to trehalose by more than 500-fold. Furthermore, dietary trehalose increases the virulence of a RT027 strain in a mouse model of infection. RT078 strains acquired a cluster of four genes involved in trehalose metabolism, including a PTS permease that is both necessary and sufficient for growth on low concentrations of trehalose. We propose that the implementation of trehalose as a food additive into the human diet, shortly before the emergence of these two epidemic lineages, helped select for their emergence and contributed to hypervirulence.

The effects of sugar-sweetened (SSB) and non-nutritive sweetened (NSB) beverages on the regulation of appetite, energy intake and body weight regulation remain controversial. Using a behavioral choice paradigm, we sought to determine the effects of consuming a SSB or NSB on appetite and the reinforcing value of sweet relative to salty/savory snack foods. In a randomized crossover study, 21 healthy weight adults consumed 360 ml of SSB (sucrose; 31 g) or NSB (sucralose; 4 g) with a standardized meal. Hedonic ratings for the sweet and salty/savory snack foods used for the reinforcement task were assessed prior to the start of the study. Satiety and the desire to eat foods with a specific taste profile were assessed before and every 30 min post-meal for 4 h. The relative reinforcing value of the snack foods was assessed using a computer-based choice task (operant responding with concurrent schedules of reinforcement) 4 h post-meal. Hedonic ratings did not differ between the most highly liked sweet and salty/savory snack foods. Beverage type did not influence measures of satiety or the desire to eat foods with a specific taste. However, sweet snacks were more (p < 0.05) reinforcing relative to salty/savory snack foods after consuming a NSB than after a SSB. In conclusion, this is the first study to demonstrate that NSB can increase the motivation to gain access to sweet snacks relative to salty/savory snack foods later in the day., (Published by Elsevier Ltd.)

Scope: Maple syrup contains various polyphenols and we investigated the effects of a polyphenol-rich maple syrup extract (MSXH) on the physiology of mice fed a high-fat diet (HFD)., Methods and Results: The mice fed a low-fat diet (LFD), an HFD, or an HFD supplemented with 0.02% (002MSXH) or 0.05% MSXH (005MSXH) for 4 weeks. Global gene expression analysis of the liver was performed, and the differentially expressed genes were classified into three expression patterns; pattern A (LFD < HFD > 002MSXH = 005MSXH, LFD > HFD < 002MSXH = 005MSXH), pattern B (LFD < HFD = 002MSXH > 005MSXH, LFD > HFD = 002MSXH < 005MSXH), and pattern C (LFD < HFD > 002MSXH < 005MSXH, LFD > HFD < 002MSXH > 005MSXH). Pattern A was enriched in glycolysis, fatty acid metabolism, and folate metabolism. Pattern B was enriched in tricarboxylic acid cycle while pattern C was enriched in gluconeogenesis, cholesterol metabolism, amino acid metabolism, and endoplasmic reticulum stress-related event., Conclusion: Our study suggested that the effects of MSXH ingestion showed (i) dose-dependent pattern involved in energy metabolisms and (ii) reversely pattern involved in stress responses., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background/objective: Excessive fructose intake has been linked to hyperuricaemia. Our aim was to test whether 355 and 600 ml of commercial sugar-sweetened soft drinks would acutely raise plasma uric acid., Subjects/methods: Forty-one participants were randomised to a control group or an intervention group. The control group consumed 600 ml of fructose and 600 ml of glucose beverages. The soft drink group consumed 355 and 600 ml of beverages in random order. The control beverages were matched for fructose content with 600 ml of soft drink (26.7 g). Blood samples were collected at baseline, 30 and 60 min and analysed for plasma uric acid., Results: Plasma uric acid concentrations were 13 (95% confidence interval: (CI): 3, 23) and 17 μmol/l (95% CI: 6, 28) higher 30 and 60 min after consumption of 600 ml of soft drink compared with the glucose control. The corresponding values for the fructose beverage were 22 (95% CI: 16, 29) and 23 μmol/l (95% CI: 14, 33). There was no significant difference in the increase in uric acid following the 600-ml soft drink compared with the fructose control at 30 min (6 μmol/l; 95% CI: -4, 15) or 60 min (5 μmol/l; 95% CI: -7, 17). There was no difference in the uric-acid-raising effect between the 355 and 600 ml volumes at 30 min (-1 μmol/l; 95% CI: -9, 6) or 60 min (-5 μmol/l; 95% CI: -10, 1)., Conclusion: Small and transient increases in plasma uric acid are likely after consumption of sucrose-sweetened commercially available single-serve soft drinks in volumes as small as 355 ml.