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OBJECTIVES: To evaluate the association between percent body fat (%BF) and body mass index (BMI) among BMI-defined non-obese individuals between 40 and 69 years of age using a population-based Canadian sample. DATA AND METHODS: Cross-sectional data from the Canadian Health Measures Survey (2007 and 2009) was used to select all middle-aged individuals with BMI < 30 kg/m 2 ( n = 2,656). %BF was determined from anthropometric skinfolds and categorized according to sex-specific equations. Association of other anthropometry measures and metabolic markers were evaluated across different %BF categories. Significance of proportions was evaluated using chi-squared and Bonferroni-adjusted Wald test. Diagnostic performance measures of BMI-defined overweight categories compared to those defined by %BF were reported. RESULTS: The majority (69%) of the sample was %BF-defined overweight/obese, while 55% were BMI-defined overweight. BMI category was not concordant with %BF classification for 30% of the population. The greatest discordance between %BF and BMI was observed among %BF-defined overweight/obese women (32%). Sensitivity and specificity of BMI-defined overweight compared to %BF-defined overweight/obese were (58%, 94%) among females and (82%, 59%) among males respectively. According to the estimated negative predictive value, if an individual is categorized as BMI-defined non-obese, he/she has a 52% chance of being in the %BF-defined overweight/obese category. CONCLUSION: Middle-aged individuals classified as normal by BMI may be overweight/obese based on measures of %BF. These individuals may be at risk for chronic diseases, but would not be identified as such based on their BMI classification. Quantifying %BF in this group could inform targeted strategies for disease prevention.

Background and aims Non-alcoholic fatty liver disease is now the leading liver disease in North America. The progression of non-alcoholic fatty liver disease to the inflammatory condition, non-alcoholic steatohepatitis is complex and currently not well understood. Intestinal microbial dysbiosis has been implicated in the development of non-alcoholic fatty liver disease and progression of non-alcoholic steatohepatitis. Volatile organic compounds are byproducts of microbial metabolism in the gut that may enter portal circulation and have hepatotoxic effects contributing to the pathogenesis of non-alcoholic steatohepatitis. To test this hypothesis, we measured volatile organic compounds in cecal luminal contents and portal venous blood in a mouse model of non-alcoholic steatohepatitis. Methods Gas chromatography–mass spectrometry analysis was conducted on cecal content and portal vein blood for volatile organic compound detection from mice fed a methionine and choline deficient diet, which induces non-alcoholic steatohepatitis. The colonic microbiome was studied by 16S rRNA gene amplification using the Illumina MiSeq platform. Results Sixty-eight volatile organic compounds were detected in cecal luminal content, a subset of which was also present in portal venous blood. Importantly, differences in portal venous volatile organic compounds were associated with diet-induced steatohepatitis establishing a biochemical link between gut microbiota-derived volatile organic compounds and increased susceptibility to non-alcoholic steatohepatitis. Conclusion Our model creates a novel tool to further study the role of gut-derived volatile organic compounds in the pathogenesis of non-alcoholic steatohepatitis.

Background: Prebiotics have been shown to improve satiety in adults with overweight and obesity; however, studies in children are limited.Objective: We examined the effects of prebiotic supplementation on appetite control and energy intake in children with overweight and obesity.Design: This study was a randomized, double-blind, placebo-controlled trial. Forty-two boys and girls, ages 7-12 y, with a body mass index (BMI) of ≥85th percentile were randomly assigned to 8 g oligofructose-enriched inulin/d or placebo (maltodextrin) for 16 wk. Objective measures of appetite included energy intake at an ad libitum breakfast buffet, 3-d food records, and fasting satiety hormone concentrations. Subjective appetite ratings were obtained from visual analog scales before and after the breakfast. Children's Eating Behavior Questionnaires were also completed by caregivers.Results: Compared with placebo, prebiotic intake resulted in significantly higher feelings of fullness (P = 0.04) and lower prospective food consumption (P = 0.03) at the breakfast buffet at 16 wk compared with baseline. Compared with placebo, prebiotic supplementation significantly reduced energy intake at the week 16 breakfast buffet in 11- and 12-y-olds (P = 0.04) but not in 7- to 10-y-olds. Fasting adiponectin (P = 0.04) and ghrelin (P = 0.03) increased at 16 wk with the prebiotic compared with placebo. In intent-to-treat analysis, there was a trend for prebiotic supplementation to reduce BMI z score to a greater extent than placebo (-3.4%; P = 0.09) and a significant -3.8% reduction in per-protocol analysis (P = 0.043).Conclusions: Independent of other lifestyle changes, prebiotic supplementation in children with overweight and obesity improved subjective appetite ratings. This translated into reduced energy intake in a breakfast buffet in older but not in younger children. This simple dietary change has the potential to help with appetite regulation in children with obesity. This trial was registered at clinicaltrials.gov as NCT02125955.

Wedged insoles are believed to be of clinical benefit to individuals with knee osteoarthritis by reducing the knee adduction moment (KAM) during gait. However, previous clinical trials have not specifically controlled for KAM reduction at baseline, thus it is unknown if reduced KAMs actually confer a clinical benefit. Forty-eight participants with medial knee osteoarthritis were randomly assigned to either a control group where no footwear intervention was given, or a wedged insole group where KAM reduction was confirmed at baseline. KAMs, Knee Injury and Osteoarthritis Outcome Score (KOOS) and Physical Activity Scale for the Elderly (PASE) scores were measured at baseline. KOOS and PASE surveys were re-administered at three months follow-up. The wedged insole group did not experience a statistically significant or clinically meaningful change in KOOS pain over three months (p=0.173). Furthermore, there was no association between change in KAM magnitude and change in KOOS pain over three months within the wedged insole group (R

The microbiota, the entirety of microorganisms residing in the gut, is increasingly recognized as an environmental factor in the maintenance of health and the development of disease. The objective of this analysis was to model in vivo interactions between gut microbiota and both serum and liver metabolites. Different genotypic models (C57BL/6 and BTBR(T+tf/j) mice) were studied in combination with significant dietary manipulations (chow vs ketogenic diets) to perturb the gut microbiota. Diet rather than genotype was the primary driver of microbial changes, with the ketogenic diet diminishing total bacterial levels. Fecal but not cecal microbiota profiles were associated with the serum and liver metabolomes. Modeling metabolome-microbiota interactions showed fecal Clostridium leptum to have the greatest impact on host metabolism, significantly correlating with 10 circulating metabolites, including 5 metabolites that did not correlate with any other microbes. C. leptum correlated negatively with serum ketones and positively with glucose and glutamine. Interestingly, microbial groups most strongly correlated with host metabolism were those modulating gut barrier function, the primary site of microbe-host interactions. These results show very robust relationships and provide a basis for future work wherein the compositional and functional associations of the microbiome can be modeled in the context of the metabolome.

The novel polysaccharide (NPS) PolyGlycopleX (PGX) has been shown to reduce glycemia. Pharmacological treatment with sitagliptin, a dipeptidyl peptidase 4 (DPP4) inhibitor, also reduces glycemia by increasing glucagon-like peptide-1 (GLP-1). Our objective was to determine if using NPS in combination with sitagliptin reduces hyperglycemia in Zucker diabetic fatty (ZDF) rats more so than either treatment alone. Male ZDF rats were randomized to: 1) cellulose/vehicle [control (C)]; 2) NPS (5% wt:wt)/vehicle (NPS);3) cellulose/sitagliptin [10 mg/(kg d) (S)]; or4) NPS (5%) + S [10 mg/(kg d) (NPS+S)]. Glucose tolerance, adiposity, satiety hormones, and mechanisms related to DPP4 activity and hepatic and pancreatic histology were examined. A clinically relevant reduction in hyperglycemia occurred in the rats treated with NPS+S (P = 0.001) compared with NPS and S alone. Blood glucose, measured weekly in fed and feed-deprived rats and during an oral glucose tolerance test, was lower in the NPS+S group compared with all other groups (all P = 0.001). At wk 6, glycated hemoglobin was lower in the NPS+S group than in the C and S (P = 0.001) and NPS (P = 0.06) groups. PGX (P = 0.001)and S (P= 0.014) contributed to increased lean mass. Active GLP-1 was increasedby S (P = 0.001) and GIP was increased by NPS (P = 0.001). Plasma DPP4 activity was lower in the NPS+S and S groups than in the NPS and C groups (P = 0.007). Insulin secretion and b-cell mass was increased with NPS ( P< 0.05). NPS alone reduced LDL cholesterol and hepatic steatosis (P < 0.01). Independently, NPS and S improve several metabolic outcomes in ZDF rats, but combined, their ability to markedly reduce glycemia suggests they may be a promising dietary/pharmacological co-therapy for type 2 diabetes management. J. Nutr. doi: 10.3945/jn.112.163204.

Large differences in the composition of diet between early development and adulthood can have detrimental effects on obesity risk. We examined the effects of an intermittent high fat/sucrose diet (HFS) on satiety hormone and serum metabolite response in disparate diets. Wistar rat pups were fed control (C), high prebiotic fiber (HF) or high protein (HP) diets (weaning to 16 weeks), HFS diet challenged (6 weeks), and finally reverted to their respective C, HF, or HP diet (4 weeks). At conclusion, measurement of body composition and satiety hormones was accompanied by 1H NMR metabolic profiles in fasted and postprandial states. Metabolomic profiling predicted dietary source with >90% accuracy. The HF group was characterized by lowest body weight and body fat (P < 0.05) and increased satiety hormone levels (glucagon-like peptide 1 and peptide-YY). Regularized modeling confirmed that the HF diet is associated with higher gut hormone secretion that could reflect the known effects of prebiotics on gut microbiota and their fementative end products, the short chain fatty acids. Rats reared on a HF diet appear to experience fewer adverse effects from an intermittent high fat diet in adulthood when rematched to their postnatal diet. Metabolite profiles associated with the diets provide a distinct biochemical signature of their effects.

Energy balance is controlled by centres of the brain which receive important inputs from the gastrointestinal tract, liver, pancreas, adipose tissue and skeletal muscle, mediated by many different signalling molecules. Obesity occurs when control of energy intake is not matched by the degree of energy expenditure. Obesity is not only a state of disordered energy balance it is also characterized by systemic inflammation. Systemic inflammation is triggered by the leakage of bacterial lipopolysaccharide through changes in intestinal permeability. The endocannabinoid system, consisting of the cannabinoid receptors, endogenous cannabinoid ligands and their biosynthetic and degradative enzymes, plays vital roles in the control of energy balance, the control of intestinal permeability and immunity. In this review we will discuss how the endocannabinoid system, intestinal microbiota and the brain-gut axis are involved in the regulation of energy balance and the development of obesity-associated systemic inflammation. Through direct and indirect actions throughout the body, the endocannabinoid system controls the development of obesity and its inflammatory complications.

How to cite this article Reimer R.A., Pelletier X., Carabin I.G., Lyon M.R., Gahler R.J. & Wood S. (2012) Faecal short chain fatty acids in healthy subjects participating in a randomised controlled trial examining a soluble highly viscous polysaccharide versus control. J Hum Nutr Diet. 25, 373–377 Abstract Background: Short chain fatty acids (SCFA) are produced by the bacterial fermentation of dietary fibre and have been linked with intestinal health. The present study examined faecal SCFA concentrations in subjects consuming a novel soluble highly viscous polysaccharide (HVP) or control for 3 weeks. A total of 54 healthy adults participated in a randomised, double-blind, placebo-controlled study. Methods: Subjects were randomised to consume HVP or control (skim milk powder). A dose of 5 g day−1 was consumed in the first week, followed by 10 g day−1 in the second and third weeks (n = 27 per group). The primary outcome was SCFA concentrations in faecal samples collected at baseline (visit 1, V1), at 1 week (V2) and at 3 week (V3). Results: The reduction in faecal acetate from V1 to V3 in control subjects was not observed in subjects consuming HVP. There were no differences in propionate, butyrate, valerate or caproate concentrations. There was a significant treatment effect (P = 0.03) for total SCFA, with higher concentrations observed in subjects consuming HVP versus control. Conclusions: HVP is a viscous functional fibre that may influence gut microbial fermentation. Further work is warranted to examine the fermentative properties of HVP and possible links with appetite regulation and reduced serum low-density lipoprotein cholesterol concentrations.

Non-alcoholic fatty liver disease (NAFLD) and the more severe non-alcoholic steatohepatitis (NASH) represent a spectrum of diseases involving hepatic fat accumulation and histological features essentially identical to alcoholic liver disease; however, they occur in the absence of excessive alcohol intake. They typically arise in conjunction with one or more features of the metabolic syndrome. Lifestyle mediated weight loss remains the primary mode of therapy for NAFLD and NASH, but this is often ineffective and adjunctive medical and surgical treatments are presently lacking. Prebiotic fibres are a group of non-digestible carbohydrates that modulate the human microbiota in a manner that is advantageous to host health. Rodent studies suggest that dietary supplementation with prebiotic fibres positively impacts NAFLD by modifying the gut microbiota, reducing body fat, and improving glucoregulation. Future research should focus on placebo-controlled, human, clinical trials using histological endpoints to address the effects of prebiotics on NAFLD and NASH. The aim of this review is to summarize current knowledge about prebiotics as an emerging therapeutic target for NAFLD.

Regular coffee consumption significantly lowers the risk of type 2 diabetes (T2D). Coffee contains thousands of compounds; however, the specific component(s) responsible for this reduced risk is unknown. Chlorogenic acids (CGA) found in brewed coffee inhibit intestinal glucose uptake in vitro. The objective of this study was to elucidate the mechanisms by which CGA acts to mediate blood glucose response in vivo. Conscious, unrestrained, male Sprague–Dawley rats were chronically catheterized and gavage-fed a standardized meal (59% carbohydrate, 25% fat, 12% protein), administered with or without CGA (120 mg·kg–1), in a randomized crossover design separated by a 3-day washout period. Acetaminophen was co-administered to assess the effects of CGA on gastric emptying. The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were measured. GLP-1 response in the presence of glucose and CGA was further examined, using the human colon cell line NCI-H716. Total area under the curve (AUC) for blood glucose was significantly attenuated in rats fed CGA (p < 0.05). Despite this, no differences in plasma insulin or nonesterified fatty acids were observed, and gastric emptying was not altered. Plasma GIP response was blunted in rats fed CGA, with a lower peak concentration and AUC up to 180 min postprandially (p < 0.05). There were no changes in GLP-1 secretion in either the in vivo or in vitro study. In conclusion, CGA treatment resulted in beneficial effects on blood glucose response, with alterations seen in GIP concentrations. Given the widespread consumption and availability of coffee, CGA may be a viable prevention tool for T2D.

Aims The effects of the novel water soluble, viscous fiber complex PolyGlycopleX® [(α- d -glucurono-α- d -manno-β- d -manno-β- d -gluco), (α- l -gulurono-β- d mannurono), β- d -gluco-β- d -mannan (PGX®)] on body weight, food consumption, glucose, insulin, and glucagon-like peptide (GLP-1) levels were determined in Zucker diabetic rats (ZDFs). Such fibers are thought to improve glycemic control through increased GLP-1 induced insulin secretion. Main methods ZDFs were treated 12 weeks with normal rodent chow supplemented with cellulose (control, inert fiber), inulin or PGX® at 5% wt/wt and effects on body weight, glycemic control, and GLP-1 determined. Key findings In the fed state, PGX® reduced blood glucose compared to the other groups from week 5 until study termination while insulin was significantly elevated when measured at week 9, suggesting an insulin secretagogue effect. Fasting blood glucose was similar among groups until 7–8 weeks when levels began to climb with a modest reduction caused by PGX®. An oral glucose tolerance test in fasted animals (week 11) showed no change in insulin sensitivity scores among diets, suggesting an insulinotropic effect for PGX® rather than increased insulin sensitivity. PGX® increased plasma levels of GLP-1, while HbA 1c was markedly reduced by PGX®. Body weights were not changed despite a significant reduction in food consumption induced by PGX® up to week 8 when the PGX®-treated group showed an increase in body weight despite a continued reduction in food consumption. Significance PGX® improved glycemic control and reduced protein glycation, most likely due to the insulin secretagogue effects of increased GLP-1.

The aim of this study was to determine if the neutral cannabinoid CB 1 receptor antagonist, AM4113, regulates body weight in the rat via changes in food intake. We confirmed that the AM4113-induced reduction in food intake is mediated by CB 1 receptors using CB 1 receptor knockout mice. In rats, intraperitoneally administered AM4113 (2, 10 mg kg −1 ) had a transient inhibitory effect on food intake, while body weight gain was suppressed for the duration of the study. AM4113-induced hypophagia was no longer observed once the inhibitory effect of AM4113 on body weight stabilized, at which time rats gained weight at a similar rate to vehicle-treated animals, yet at a lower magnitude. Pair-feeding produced similar effects to treatment with AM4113. Food intake and body weight gain were also inhibited in rats by oral administration of AM4113 (50 mg kg −1 ). Dual energy x-ray absorptiometry (DEXA) was used to measure lean and fat mass. The AM4113 treated group had 29.3 ± 11.4% lower fat mass than vehicle-treated rats; this trend did not reach statistical significance. There were no differences in circulating levels of the endogenous cannabinoid 2-arachidonoyl glycerol (2-AG), glucose, triglycerides, or cholesterol observed between treatment groups. Similarly, 2-AG hypothalamic levels were not modified by AM4113 treatment. These data suggest that blockade of an endocannabinoid tone acting at CB 1 receptors induces an initial, transient reduction in food intake which results in long-term reduction of body weight gain.

The primary objective of this study was to explore the macro- and micro-nutrient intakes and dietary patterns of patients with Crohn&rsquo, s disease (CD). Secondary objectives were to (a) compare the micronutrient intakes of CD patients with a representative sample of individuals, (b) describe the macro- and micronutrient intakes of male and female CD patients, and (c) describe Mediterranean diet scores (P-MDS) of male and female CD patients in remission that were recruited from an inflammatory bowel disease (IBD) clinic in Calgary, AB. Consecutive patients with ileal and/or colonic CD in endoscopic remission were recruited for participation in this cross-sectional study. Sixty-seven patients were enrolled with a mean age of 45, and a Body Mass Index (BMI) &ge, 25. Compared with the representative sample, patients with CD had similar energy, protein, carbohydrate, and total fat intake. However, polyunsaturated fats (PUFA), omega-6 and 3, and monounsaturated fats (MUFA) were lower in CD patients and dietary fiber intake was higher (p &lt, 0.05). Vitamins C, D, thiamin, niacin, magnesium, phosphorus, zinc, and potassium were all significantly lower in all CD patients when compared to the representative sample (p &lt, 0.05). Few patients with CD met the P-MDS criteria and overall scores were low (mean 4.5, Standard Deviation (SD) = 1.1 in males and 4.7, SD = 1.8 in females). The CD patients in this study had suboptimal dietary intakes and patterns and these data may be used to inform future dietary interventions in this population to improve intake.

A systematic evaluation of the effects of calcium (Ca) and protein source on food intake and taste aversion (TA) in rats is lacking. The purpose of this research was twofold: (1) to determine if Sprague-Dawley rats display TA to standard rat chow supplemented with 2.4% Ca and (2) to determine if short (24-hour) and long-term (weekly) food intake and weight gain are altered when rats are given access to diets containing various protein sources (casein, whey, dairy, or soy). Rats were assigned to one of two diet groups to examine high (2.4%) versus low (0.67%) Ca or to one of four groups to examine taste preference of diets where the sole protein was one of casein, soy, whey, or complete dairy. A crossover design was used to ensure rats consumed all test diets. Food intake and behavioral sequence of satiety were measured. There was no TA to the 2.4% Ca diet or to any protein source. Food intake did not differ between the two Ca diets or between the four protein diets. The dairy diet attenuated weekly weight gain compared to all other diets except whey. Overall, this study suggests that the levels of Ca and types of protein used in previous work addressing changes in body weight in rats do not influence food intake or trigger TA.

Dietary fiber reduces the intestinal absorption of nutrients and the blood concentrations of cholesterol and triglycerides.We wished to test the hypothesis that high-viscosity (HV) and low-viscosity preparations of barley and oat beta-glucan modify the expression of selected genes of lipid-binding proteins in the intestinal mucosa and reduce the intestinal in vitro uptake of lipids.Five different beta-glucan extracts were separately added to test solutions at concentrations of 0.1-0.5% (wt/wt), and the in vitro intestinal uptake of lipids into the intestine of rats was assessed. An intestinal cell line was used to determine the effect of beta-glucan extracts on the expression of intestinal genes involved in lipid metabolism and fatty acid transport.All extracts reduced the uptake of 18:2 when the effective resistance of the unstirred water layer was high. When the unstirred layer resistance was low, the HV oat beta-glucan extract reduced jejunal 18:2 uptake, while most extracts reduced ileal 18:2 uptake. Ileal 18:0 uptake was reduced by the HV barley extract, while both jejunal and ileal cholesterol uptakes were reduced by the medium-purity HV barley extract. The inhibitory effect of HV barley beta-glucan on 18:0 and 18:2 uptake was more pronounced at higher fatty acid concentrations. The expression of genes involved in fatty acid synthesis and cholesterol metabolism was down-regulated with the HV beta-glucan extracts. beta-Glucan extracts also reduced intestinal fatty-acid-binding protein and fatty acid transport protein 4 mRNA.The reduced intestinal fatty acid uptake observed with beta-glucan is associated with inhibition of genes regulating intestinal uptake and synthesis of lipids. The inhibitory effect of beta-glucan on intestinal lipid uptake raises the possibility of their selective use to reduce their intestinal absorption.

The combination of dairy protein and dietary calcium (Ca) may enhance weight loss more effectively than either compound alone. Our purpose in this study was to determine the effect of various protein sources [skim milk powder (SMP), whey, casein, and soy protein isolate (SPI)] and 2 levels of Ca [low, 0.67% Ca (LC) or high, 2.4% Ca (HC)] on weight loss. Sixty-four 12-wk-old Sprague-Dawley, diet-induced obese rats were assigned to 1 of 8 energy-restricted (ER) diets for 4 wk with 1 of the 4 protein sources and either LC or HC concentrations. Rats were ER to 70% of the ad libitum food and energy intake of a reference group (n = 8) fed the AIN-93M diet. The interaction between dietary protein and Ca affected final body weight and fat mass (FM) (P < 0.05). FM was less in rats fed SMP-HC than in those fed casein-LC or SPI-LC. Lean body mass was greater in rats fed SMP than in those fed whey. Rats fed HC diets had a lower plasma glucagon area under the curve (AUC) than those fed LC diets. The blood glucose AUC, homeostatic model of insulin resistance, and the expression of certain hepatic genes involved in energy metabolism were affected by protein and Ca. These data suggest that consuming a diet containing SMP and HC is associated with a lower FM in obese, male, ER rats than in diets containing casein or SPI and LC; however, the role of SMP and Ca in glucose homeostasis remains to be determined.

Evidence suggests that dietary calcium (Ca) and particularly dairy foods may attenuate weight gain and improve symptoms of the metabolic syndrome. The purpose of this study was to determine the effect of different Ca-enriched dairy protein sources on the prevention of weight gain in Sprague-Dawley diet-induced obese (DIO) rats. Twelve week-old DIO rats were assigned to one of eight ad libitum diets that varied in protein source (casein, whey, or complete dairy), Ca content (0.67 or 2.4%) and energy level (high fat/high sucrose (HFHS); or normal calorie density (NC)). Body composition and response to a meal tolerance test (MTT) were measured. Average daily caloric intake did not differ within normal or high energy density groups. At the end of 8 weeks, the dairy/HFHS/0.67% and 2.4% groups had significantly lower body weight than all other HFHS groups. The dairy/HFHS/0.67% and 2.4% groups also had lower body fat and greater lean mass expressed as a percent (P0.05). Homeostatic model assessment of insulin resistance (HOMA(IR)) was lowest for dairy/HFHS/0.67% and significantly different from whey/HFHS/0.67% and 2.4%. Independent of protein source, high Ca decreased plasma insulin at 30 min in the MTT more so than low Ca (P0.05). Hepatic sterol regulatory element-binding protein (SREBP1c) and peroxisome proliferator-activated receptor-gamma (PPARgamma) mRNA was downregulated by dairy and whey compared to casein in the HFHS/0.67% diets. Overall, these data suggest that complete dairy improves body composition and insulin sensitivity to a greater extent than whey or casein alone.

Prebiotic fibres have been proposed to promote weight loss and lower serum cholesterol; however, the mechanisms are not fully understood. The aim of the present research was to identify possible mechanisms through which prebiotic fibres improve serum lipids. Lean and obese JCR:La-cp rats aged 8 weeks consumed one of three diets supplemented with 0, 10 or 20 % prebiotic fibre for 10 weeks. Rats were anaesthetised and a fasting blood sample was taken for lipid analysis. Real-time PCR was used to determine gene expression for cholesterol and fatty acid regulatory genes in liver tissue. Liver and caecal digesta cholesterol and TAG content were quantified. Both doses of prebiotic fibre lowered serum cholesterol levels by 24 % in the obese hyperlipidaemic rats (P P

Rodent studies show that oligofructose promotes weight loss, stimulates satiety hormone secretion, reduces energy intake, and improves lipid profiles.Our objective was to examine the effects of oligofructose supplementation on body weight and satiety hormone concentrations in overweight and obese adults.This study was a randomized, double-blind, placebo-controlled trial. Forty-eight otherwise healthy adults with a body mass index (in kg/m2)25 were randomly assigned to receive 21 g oligofructose/d or a placebo (maltodextrin) for 12 wk. Body composition (by dual-energy X-ray absorptiometry); meal tolerance tests, including satiety hormone response; food intake; and subjective appetite ratings were determined.There was a reduction in body weight of 1.03 +/- 0.43 kg with oligofructose supplementation, whereas the control group experienced an increase in body weight of 0.45 +/- 0.31 kg over 12 wk (P = 0.01). A lower area under the curve (AUC) for ghrelin (P = 0.004) and a higher AUC for peptide YY (PYY) with oligofructose (P = 0.03) coincided with a reduction in self-reported caloric intake (Por = 0.05). Glucose decreased in the oligofructose group and increased in the control group between initial and final tests (Por = 0.05). Insulin concentrations mirrored this pattern (Por = 0.05). Oligofructose supplementation did not affect plasma active glucagon-like peptide 1 secretion. According to a visual analog scale designed to assess side effects, oligofructose was well tolerated.Independent of other lifestyle changes, oligofructose supplementation has the potential to promote weight loss and improve glucose regulation in overweight adults. Suppressed ghrelin and enhanced PYY may contribute in part to the reduction in energy intake. The trial was registered at clinicaltrials.gov as NCT00522353.

Risk of developing obesity and diabetes may be influenced by the nutritional environment early in life. We examined the effects of high fibre or protein diets on satiety hormones and genes involved in glucose and lipid metabolism during postnatal development and on adult fat mass. At 21 days of age, Wistar rat pups were weaned onto control (C), high fibre (HF) or high protein (HP) diet. Tissue and blood were collected at 7, 14, 21, 28 and 35 days after birth. A second group of rats consumed the weaning diets until 4 months when they were switched to a high fat–high sugar diet for 6 weeks, after which body and fat mass and plasma glucose were determined. In young rats, HF diet increased plasma glucagon-like peptide (GLP-1) compared to C and HP and decreased leptin compared to C at postnatal days 28 and 35. Hepatic fatty acid synthase mRNA was down-regulated by HF and HP compared to C at days 28 and 35. In brown adipose tissue, HF increased uncoupling protein-3 mRNA whereas HP increased mRNA of the inflammatory cytokine interleukin-6. Body weight, fat mass and glycaemia in adult males and fat mass in females were greater after the high fat challenge in rats that consumed the HP diet from weaning. Increasing fibre or protein in postnatal diets causes rapid change in satiety hormone secretion and genes involved in glucose and lipid metabolism which appear to influence fat mass and glycaemia in adulthood, high protein being associated with increased susceptibility to obesity.

Caffeine is a proven ergogenic aid, increasing athletic performance, endurance, and mental chronometry at doses as low as 1–3 mg·kg–1. As coffee is a readily available and commonly ingested form of caffeine, the two are often equated. However, coffee also contains hundreds of other biologically active compounds, many of which are metabolically distinct from caffeine. The purpose of this review was to examine the prevalence of coffee and (or) caffeine consumption among elite Canadian athletes, and to delineate the effects of coffee and caffeine on physical activity, weight maintenance, performance, and metabolism. A total of 270 self-reported 3-day food records were examined for caffeine intake from athletes registered with Canadian Sport Centres in 2005 and 2006. Athletes ranged in age from 16–45 years, and competed in 38 different sports. Results showed that 30% of athletes ingested >1 mg·kg–1·day–1from a variety of sources. Average daily intake was 0.85 ± 13 mg·kg–1. Caffeine intake was not correlated with any 1 sport; the 10 highest caffeine users were athletes from 9 different sports, including skill, endurance, and power sports. No differences were noted for average caffeine ingestion between summer and winter sports. High caffeine intakes corresponded to coffee ingestion, with the 25 highest individual intakes (193–895 mg·day–1) from coffee drinkers. In summary, it can be concluded that the majority of high-level Canadian athletes consume dietary caffeine primarily in the form of coffee. However, levels consumed are insufficient to elicit performance enhancement. Potential detrimental effects of caffeine consumption on exercise performance include gastric upset, withdrawal, sleep disturbance, and interactions with other dietary supplements.

Background: We have shown that individually, dietary fiber and protein increase secretion of the anorexigenic and insulinotropic hormone, glucagon-like peptide-1 (GLP-1). Objective: Our objective was to combine, in one diet, high levels of fiber and protein to maximize GLP-1 secretion, improve glucose tolerance, and reduce weight gain. Methods and Procedures: Lean (+/?) and obese (cp/cp) male James C Russell corpulent (JCR:LA-cp) rats lacking a functional leptin receptor were fed one of four experimental diets (control, high protein (HP), high fiber (HF, prebiotic fiber inulin), or combination (CB)) for 3 weeks. An oral glucose tolerance test (OGTT) was performed to evaluate plasma GLP-1, insulin and glucose. Plasma lipids and intestinal proglucagon mRNA expression were determined. Results: Energy intake was lower with the HF diet in lean and obese rats. Weight gain did not differ between diets. Higher colonic proglucagon mRNA in lean rats fed a CB diet was associated with higher GLP-1 secretion during OGTT. The HP diet significantly reduced plasma glucose area under the curve (AUC) during OGTT in obese rats, which reflected both an increased GLP-1 AUC and higher fasting insulin. Diets containing inulin resulted in the lowest plasma triglyceride and total cholesterol levels. Discussion: Overall, combining HP with HF in the diet increased GLP-1 secretion in response to oral glucose, but did not improve glucose tolerance or lipid profiles more than the HF diet alone did. We also suggest that glycemic and insulinemic response to prebiotics differ among rat models and future research work should examine their role in improving glucose tolerance in diet-induced vs. genetic obesity with overt hyperleptinemia.

Non-alcoholic fatty liver disease has become the leading liver disease in North America and is associated with the progressive inflammatory liver disease non-alcoholic steatohepatitis (NASH). Considerable effort has been made to understand the role of resident and recruited macrophage populations in NASH however numerous questions remain. Our goal was to characterize the dynamic changes in liver macrophages during the initiation of NASH in a murine model. Using the methionine-choline deficient diet we found that liver-resident macrophages, Kupffer cells were lost early in disease onset followed by a robust infiltration of Ly-6C+ monocyte-derived macrophages that retained a dynamic phenotype. Genetic profiling revealed distinct patterns of inflammatory gene expression between macrophage subsets. Only early depletion of liver macrophages using liposomal clodronate prevented the development of NASH in mice suggesting that Kupffer cells are critical for the orchestration of inflammation during experimental NASH. Increased understanding of these dynamics may allow us to target potentially harmful populations whilst promoting anti-inflammatory or restorative populations to ultimately guide the development of effective treatment strategies.

Maternal obesity and overnutrition during pregnancy and lactation can program an increased risk of obesity in offspring. In this context, improving maternal metabolism may help reduce the intergenerational transmission of obesity. Here we show that, in Sprague-Dawley rats, selectively altering obese maternal gut microbial composition with prebiotic treatment reduces maternal energy intake, decreases gestational weight gain and prevents increased adiposity in dams and their offspring. Maternal serum metabolomics analysis, along with satiety hormone and gut microbiota analysis, identified maternal metabolic signatures that could be implicated in programming offspring obesity risk and highlighted the potential influence of maternal gut microbiota on maternal and offspring metabolism. In particular, the metabolomic signature of insulin resistance in obese rats normalized when dams consumed the prebiotic. In summary, prebiotic intake during pregnancy and lactation improves maternal metabolism in diet-induced obese rats in a manner that attenuates the detrimental nutritional programming of offspring associated with maternal obesity. Overall, these findings contribute to our understanding of the maternal mechanisms influencing the developmental programming of offspring obesity and provide compelling pre-clinical evidence for a potential strategy to improve maternal and offspring metabolic outcomes in human pregnancy.

The Thrifty Phenotype Hypothesis proposes that the fetus takes cues from the maternal environment to predict its postnatal environment. A mismatch between the predicted and actual environments precipitates an increased risk of chronic disease. Our objective was to determine if, following a high fat, high sucrose (HFS) diet challenge in adulthood, re-matching offspring to their maternal gestational diet would improve metabolic health more so than if there was no previous exposure to that diet. Animals re-matched to a high prebiotic fiber diet (HF) had lower body weight and adiposity than animals re-matched to a high protein (HP) or control (C) diet and also had increased levels of the satiety hormones GLP-1 and PYY (p < 0.05). Control animals, whether maintained throughout the study on AIN-93M, or continued on HFS rather than reverting back to AIN-93M, did not differ from each other in body weight or adiposity. Overall, the HF diet was associated with the most beneficial metabolic phenotype (body fat, glucose control, satiety hormones). The HP diet, as per our previous work, had detrimental effects on body weight and adiposity. Findings in control rats suggest that the obesogenic potential of the powdered AIN-93 diet warrants investigation.

Milk, as the sole source of nutrition for the newborn mammal, provides the necessary nutrients and energy for offspring growth and development. It also contains a vast number of bioactive compounds that greatly affect the development of the neonate. The analysis of milk components will help elucidate key factors that link maternal metabolism and health with offspring growth and development. The laboratory rat represents a popular model organism for maternal studies, and rat milk can be used to examine the effect of various maternal physiological, nutritional, and pharmacological interventions on milk components, which may then impact offspring health. Here a simple method of manually collecting milk from the lactating rat that can be performed by a single investigator, does not require specialized vacuum or suction equipment, and provides sufficient milk for subsequent downstream analysis is described. A method for estimating the fat content of milk by measuring the percentage of cream within the milk sample, known as the creamatocrit, is also presented. These methods can ultimately be used to increase insight into maternal-child health and to elucidate maternal factors that are involved in proper growth and development of offspring.

Objective Acute administration of cannabinoid CB1 receptor agonists, or the ingestion of cannabis, induces short-term hyperphagia. However, the incidence of obesity is lower in frequent cannabis users compared to non-users. Gut microbiota affects host metabolism and altered microbial profiles are observed in obese states. Gut microbiota modifies adipogenesis through actions on the endocannabinoid system. This study investigated the effect of chronic THC administration on body weight and gut microbiota in diet-induced obese (DIO) and lean mice. Methods Adult male DIO and lean mice were treated daily with vehicle or THC (2mg/kg for 3 weeks and 4 mg/kg for 1 additional week). Body weight, fat mass, energy intake, locomotor activity, whole gut transit and gut microbiota were measured longitudinally. Results THC reduced weight gain, fat mass gain and energy intake in DIO but not lean mice. DIO-induced changes in select gut microbiota were prevented in mice chronically administered THC. THC had no effect on locomotor activity or whole gut transit in either lean or DIO mice. Conclusions Chronic THC treatment reduced energy intake and prevented high fat diet-induced increases in body weight and adiposity; effects that were unlikely to be a result of sedation or altered gastrointestinal transit. Changes in gut microbiota potentially contribute to chronic THC-induced actions on body weight in obesity.

Background Gastrointestinal dysfunction and gut microbial composition disturbances have been widely reported in autism spectrum disorder (ASD). This study examines whether gut microbiome disturbances are present in the BTBRT + tf/j (BTBR) mouse model of ASD and if the ketogenic diet, a diet previously shown to elicit therapeutic benefit in this mouse model, is capable of altering the profile. Findings Juvenile male C57BL/6 (B6) and BTBR mice were fed a standard chow (CH, 13 % kcal fat) or ketogenic diet (KD, 75 % kcal fat) for 10–14 days. Following diets, fecal and cecal samples were collected for analysis. Main findings are as follows: (1) gut microbiota compositions of cecal and fecal samples were altered in BTBR compared to control mice, indicating that this model may be of utility in understanding gut-brain interactions in ASD; (2) KD consumption caused an anti-microbial-like effect by significantly decreasing total host bacterial abundance in cecal and fecal matter; (3) specific to BTBR animals, the KD counteracted the common ASD phenotype of a low Firmicutes to Bacteroidetes ratio in both sample types; and (4) the KD reversed elevated Akkermansia muciniphila content in the cecal and fecal matter of BTBR animals. Conclusions Results indicate that consumption of a KD likely triggers reductions in total gut microbial counts and compositional remodeling in the BTBR mouse. These findings may explain, in part, the ability of a KD to mitigate some of the neurological symptoms associated with ASD in an animal model. Electronic supplementary material The online version of this article (doi:10.1186/s13229-016-0099-3) contains supplementary material, which is available to authorized users.

Background Evidence for the role of the gut microbiome in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is emerging. Strategies to manipulate the gut microbiota towards a healthier community structure are actively being investigated. Based on their ability to favorably modulate the gut microbiota, prebiotics may provide an inexpensive yet effective dietary treatment for NAFLD. Additionally, prebiotics have established benefits for glucose control and potentially weight control, both advantageous in managing fatty liver disease. Our objective is to evaluate the effects of prebiotic supplementation, adjunct to those achieved with diet-induced weight loss, on heptic injury and liver fat, the gut microbiota, inflammation, glucose tolerance, and satiety in patients with NAFLD. Methods/design In a double blind, placebo controlled, parallel group study, adults (BMI ≥25) with confirmed NAFLD will be randomized to either a 16 g/d prebiotic supplemented group or isocaloric placebo group for 24 weeks (n = 30/group). All participants will receive individualized dietary counseling sessions with a registered dietitian to achieve 10 % weight loss. Primary outcome measures include change in hepatic injury (fibrosis and inflammation) and liver fat. Secondary outcomes include change in body composition, appetite and dietary adherence, glycemic and insulinemic responses and inflammatory cytokines. Mechanisms related to prebiotic-induced changes in gut microbiota (shot-gun sequencing) and their metabolic by-products (volatile organic compounds) and de novo lipogenesis (using deuterium incorporation) will also be investigated. Discussion There are currently no medications or surgical procedures approved for the treatment of NAFLD and weight loss via lifestyle modification remains the cornerstone of current care recommendations. Given that prebiotics target multiple metabolic impairments associated with NAFLD, investigating their ability to modulate the gut microbiota and hepatic health in patients with NAFLD is warranted. Trial registration ClinicalTrials.gov (NCT02568605) Registered 30 September 2015

Disruption in the gut microbiota is now recognized as an active contributor towards the development of obesity and insulin resistance. This review considers one class of dietary additives known to influence the gut microbiota that may predispose susceptible individuals to insulin resistance - the regular, long-term consumption of low-dose, low calorie sweeteners. While the data are controversial, mounting evidence suggests that low calorie sweeteners should not be dismissed as inert in the gut environment. Sucralose, aspartame and saccharin, all widely used to reduce energy content in foods and beverages to promote satiety and encourage weight loss, have been shown to disrupt the balance and diversity of gut microbiota. Fecal transplant experiments, wherein microbiota from low calorie sweetener consuming hosts are transferred into germ-free mice, show that this disruption is transferable and results in impaired glucose tolerance, a well-known risk factor towards the development of a number of metabolic disease states. As our understanding of the importance of the gut microbiota in metabolic health continues to grow, it will be increasingly important to consider the impact of all dietary components, including low calorie sweeteners, on gut microbiota and metabolic health.

Obesity, and corresponding chronic-low grade inflammation, is associated with the onset and progression of knee OA. The origin of this inflammation is poorly understood. Here, the effect of high fat, high sucrose (HFS) diet induced obesity (DIO) on local (synovial fluid), and systemic (serum) inflammation is evaluated after a 12-week obesity induction and a further 16-week adaptation period. For 12-weeks of obesity induction, n = 40 DIO male Sprague-Dawley rats consumed a HFS diet while the control group (n = 14) remained on chow. DIO rats were allocated to prone (DIO-P, top 33% based on weight change) or resistant (DIO-R, bottom 33%) groups at 12-weeks. Animals were euthanized at 12- and after an additional 16-weeks on diet (28-weeks). At sacrifice, body composition and knee joints were collected and assessed. Synovial fluid and sera were profiled using cytokine array analysis. At 12-weeks, DIO-P animals demonstrated increased Modified Mankin scores compared to DIO-R and chow (p = 0.026), and DIO-R had higher Mankin scores compared to chow (p = 0.049). While numerous systemic and limited synovial fluid inflammatory markers were increased at 12-weeks in DIO animals compared to chow, by 28-weeks there were limited systemic differences but marked increases in local synovial fluid inflammatory marker concentrations. Metabolic OA may manifest from an initial systemic inflammatory disturbance. Twelve weeks of obesity induction leads to a unique inflammatory profile and induction of metabolic OA which is altered after a further 16-weeks of obesity and HFS diet intake, suggesting that obesity is a dynamic, progressive process. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1010-1018, 2016.

Patients with head and neck cancer experience loss of weight and muscle mass, decreased functioning, malnutrition, depression, and declines in quality of life during and after treatment. The purpose of this exploratory randomized study was to determine the optimal timing for the initiation of a lifestyle and progressive resistance exercise training intervention (during or after radiation therapy), as determined by intervention adherence and by comparing between-group outcomes across 24 weeks.Sixty patients with head and neck cancer were randomized to engage in a 12-week lifestyle intervention and progressive resistance-training program either during radiation treatment or immediately after completion. The primary outcome of body composition--specifically, lean body mass, body mass index, and body fat--as well as secondary outcomes of fitness, quality of life, depression, and nutrition status were evaluated.The progressive resistance-training intervention carried out during treatment did not significantly influence the primary outcome of body composition, despite a significant increase in weekly physical activity reported by the intervention group. A small-to-medium intervention effect was noted for some secondary outcomes, including fitness, quality of life, and nutrition status. Regardless of whether patients received the immediate or delayed progressive resistance-training intervention, the analysis revealed a main effect of time on body composition, fitness, quality of life, depression, and nutritional scores.Although the intervention during treatment did not reduce the loss of lean body mass, delaying the exercise program until after treatment completion was associated with improved intervention adherence, a finding with important clinical implications.

Cecal microbiota from type 2 diabetic (db/db) and control (db/(+)) mice was obtained following 6 weeks of sedentary or exercise activity. qPCR analysis revealed a main effect of exercise, with greater abundance of select Firmicutes species and lower Bacteroides/Prevotella spp. in both normal and diabetic exercised mice compared with sedentary counterparts. Conversely, Bifidobacterium spp. was greater in exercised normal but not diabetic mice (exercise × diabetes interaction). How exercise influences gut microbiota requires further investigation.

Childhood obesity has dramatically increased. Unfortunately, excess weight tends to persist into adulthood therefore therapies which target childhood obesity are essential in halting the obesity ep...

Introduction: It is well documented that athletes report greater dietary supplement (DS) usage than nonathletes; however, limited data exist for Canadian athletes, especially relative to competitive performance levels. Purpose: This descriptive and analytical, cross-sectional research investigated DS practices and opinions, preferred means for DS education, and antidoping opinions among elite Canadian athletes competing at various performance levels. Methods: Subjects completed a validated questionnaire by recall. Combined, 582 high-performance athletes (314 M, 268 F) between the ages of 11 and 42 yr (mean 19.96 +/- 3.91 yr) and representing 27 sports activities participated. Respondents were categorized into five competitive performance levels: provincial (68), national (101), North America (61), international or professional (89), and varsity (263). Results: Overall, most (88.4%) reported taking one or more DS during the previous 6 months (mean 3.08 +/- 1.87 DS per user). From a total of 1555 DS declared, sport drinks (22.4%), sport bars (14.0%), multivitamins and minerals (13.5%), protein supplements (9.0%), and vitamin C (6.4%) were most frequently reported. Athletes at the highest performance level were significantly more likely to use protein supplements, to be advised by strength trainers regarding DS usage, to have a higher self-rating of their diet, to prefer individual interviews for DS educational purposes, to perceive greater awareness of antidoping legislation, and train more h[middle dot]wk-1. Furthermore, differences were observed for the types of DS reported and justifications for use. Conclusion: This dataset, the first of its kind in Canada, was generated with a validated and reliable questionnaire and has the potential to be extended nationally and internationally to provide greater insight into the patterns and opinions of elite athletes regarding supplementation and antidoping

The lipogenic pathway has been extensively studied in rodent hepatocytes but poorly studied in human cells. This study examined the effect of glucose and hormones on fatty acid synthase (FAS) gene expression and intracellular lipid synthesis in a human hepatocyte cell line (T-9A4 cells). In low passage cells expressing glucose transporter type 2 (GLUT2) mRNA, FAS mRNA expression and triacylglycerol (TAG) synthesis increased in response to glucose and the presence of insulin and triiodothyronine (T 3 ). With increasing passages, the cells no longer expressed the GLUT2 gene, and levels of FAS mRNA were consistently elevated compared to GLUT2 (+) cells. Triglyceride synthesis was also consistently higher in the GLUT2 (−) cells. Glucose-6-phosphate (G-6-P) was constitutively high in GLUT2 (−) cells but increased in response to glucose in GLUT2 (+) cells. In the absence of GLUT2, glucose may be trapped in cells, continuously fueling the generation of G-6-P or subsequent metabolic intermediates that promote FAS gene transcription.

BACKGROUND: Patients with Crohn’s Disease (CD) are at increased risk of nutritional deficiencies that are multifactorial in etiology, and may include poor dietary diversity. Short chain fatty acids (SCFA) are known to have anti-inflammatory properties. Nutrition status and dietary diversity have been shown to impact the gut microbiome, however the effect of dietary diversity on fecal SCFA composition in CD is understudied. AIMS: (1) To describe the baseline fecal SCFA profiles in patients with CD in remission who consume a diversified diet (DD) compared to patients who consume a non-diversified diet (NDD); (2) To describe the changes in fecal SCFA in patients with CD in remission who consume a NDD following a 3-month dietary intervention. METHODS: Patients with CD were recruited prospectively at the University of Calgary. All patients were in remission as confirmed by ileo-colonoscopy within 6 months of study entry and normal fecal calprotectin levels. A NDD was defined as fewer than 3 daily servings of fruits and vegetables, dietary fiber ≤ 15g/day, red meat intake ≥ 3 weekly servings. Patients recorded dietary intake using a 3-day food record that was analyzed by the study Registered Dietitian. Patients consuming a NDD were provided a personalized dietary intervention by the RD for 3 months to improve dietary diversity and maintained weekly food diaries to assess compliance. SCFA were measured in stool samples at baseline and after 3 months by gas chromatography. RESULTS: Twenty participants were recruited (14 DD, females: n=11; 6 NDD, females: n=4). Compared with the CD group consuming a DD group at baseline, CD patients consuming a NDD had lower levels of fecal propionate (µmol/ml) (1.56 ± 0.59 vs 2.35 ± 0.18; p=0.08), lower levels of iso-butyrate (0.12 ± 0.05 vs 0.24 ± 0.02; p=0.03), and iso-valeric acid (0.15 ± 0.06 vs 0.36 ± 0.04; p=0.01). Following a 3-month dietary intervention, a significant increase in fecal propionate was observed from baseline to 3-months (1.56 ± 0.59 vs. 2.06 ± 0.55; p

Background Knee osteoarthritis (OA) progression has been linked to increased peak external knee adduction moments (KAMs). Although some trials have attempted to reduce pain and improve function in OA by reducing KAMs with a wedged footwear insole intervention, KAM reduction has not been specifically controlled for in trial designs, potentially explaining the mixed results seen in the literature. Therefore, the primary purpose of this trial is to identify the effects of reduced KAMs on knee OA pain and function. Methods/design Forty-six patients with radiographically confirmed diagnosis medial knee OA will be recruited for this 3 month randomized controlled trial. Recruitment will be from Alberta and surrounding areas. Eligibility criteria include being between the ages of 40 and 85 years, have knee OA primarily localized to the medial tibiofemoral compartment, based on the American College of Rheumatology diagnostic criteria and be classified as having a Kellgren-Lawrence grade of 1 to 3. Patients will visit the laboratory at baseline for testing that includes dual x-ray absorptiometry, biomechanical testing, and surveys (KOOS, PASE activity scale, UCLA activity scale, comfort visual analog scale). At baseline, patients will be randomized to either a wedged insole group to reduce KAMs, or a waitlist control group where no intervention is provided. The survey tests will be repeated at 3 months, and response to wedged insoles over 3 months will be evaluated. Discussion This study represents the first step in systematically evaluating the effects of reduced KAMs on knee OA management by using a patient-specific wedged insole prescription procedure rather than providing the same insole to all patients. The results of this trial will provide indications as to whether reduced KAMs are an effective strategy for knee OA management, and whether a personalized approach to footwear insole prescription is warranted. Trial registration NCT02067208. Electronic supplementary material The online version of this article (doi:10.1186/1471-2474-15-405) contains supplementary material, which is available to authorized users.

Oligofructose (OFS) is a prebiotic that reduces energy intake and fat mass via changes in gut satiety hormones and microbiota. The effects of OFS may vary depending on predisposition to obesity. The aim of this study was to examine the effect of OFS in diet-induced obese (DIO) and diet-resistant (DR) rats.Adult, male DIO, and DR rats were randomized to: high-fat/high-sucrose (HFS) diet or HFS diet + 10% OFS for 6 weeks. Body composition, food intake, gut microbiota, plasma gut hormones, and cannabinoid CB(1) receptor expression in the nodose ganglia were measured.OFS reduced body weight, energy intake, and fat mass in both phenotypes (P 0.05). Select gut microbiota differed in DIO versus DR rats (P 0.05), the differences being eliminated by OFS. OFS did not modify plasma ghrelin or CB(1) expression in nodose ganglia, but plasma levels of GIP were reduced and PYY were elevated (P 0.05) by OFS.OFS was able to reduce body weight and adiposity in both prone and resistant obese phenotypes. OFS-induced changes in gut microbiota profiles in DIO and DR rats, along with changes in gut hormone levels, likely contribute to the sustained lower body weights.

Maternal protein restriction (PR) during pregnancy is known to have numerous adverse effects on offspring, including increased adiposity and impaired glucose tolerance later in life. A few studies have shown that this adverse programming can be reversed by dietary or hormonal therapies early in postnatal life. The objective of this study was to determine if a weaning diet high in prebiotic fiber could mitigate some of the negative effects of maternal PR, such as increased adiposity and impaired glucose tolerance. Wistar rats were fed a low- (8%) or normal- (20%) protein diet during pregnancy. Male and female pups were weaned onto control (C; 5% fiber, 20% protein) or high (prebiotic) fiber (HF; 21% wt:wt, 1:1 ratio oligofructose and inulin at 4-10 wk; 10% wt:wt, 1:1 ratio oligofructose and inulin at 10-24 wk; 17.3% protein) diets. At 24 wk of age, glucose tolerance, body composition, satiety hormones, gut microbiota, and markers of intestinal permeability were measured in the offspring. Maternal PR reduced offspring birth weight by 5% and lean mass by 9% compared with the C offspring (P0.007). HF-fed offspring had lower body weights and percentage body fat (∼23% in males, ∼19% in females) at 24 wk than did C offspring (P0.02). Compared with C pups, pups fed the HF diet had greater cecal Bifidobacterium spp. (5-fold) and plasma concentrations of the gut trophic hormone glucagon-like peptide 2 (GLP-2) (P0.05). In male PR offspring fed the HF diet, insulin resistance measured by the homeostasis model assessment of insulin resistance was reduced by 81% compared with those fed the C diet (P = 0.02). In female PR offspring fed the HF diet, plasma endotoxin was greater and colonic tight junction protein 1 (Tjp1) expression was lower than in those fed the C diet. A high prebiotic fiber weaning diet mitigated increased adiposity and insulin resistance associated with maternal PR, which could improve health and decrease risk of chronic disease in offspring born to malnourished dams. However, the functional importance of sex-specific changes in markers of intestinal barrier function warrants further investigation.

A mismatch between early developmental diet and adulthood may increase obesity risk. Our objective was to determine the effects of re-matching rats to their weaning diets high in protein or fiber after transient high-fat/high-sucrose challenge in adulthood. We hypothesize that a long-term high fiber diet will be associated with a gut microbiota and hepatic gene expression reflective of reduced adiposity. Wistar rat pups were fed a control (C), high prebiotic fiber (HF), or high protein (HP) diet from 3-15 weeks of age; a high-fat/high-sucrose diet from 15-21 weeks; their respective C, HF, or HP diets from 21-25 weeks. Gut microbiota of cecal contents and hepatic gene expression were measured when rats were terminated at 25 weeks of age. HF rats had higher total bacteria, bifidobacteria and Bacteroides/Prevotella spp than C and HP at 25 weeks (P0.05). Firmicutes, especially Clostridium leptum, decreased in HF compared to C and HP (P.05). The ratio of Firmicutes:Bacteroidetes was markedly lower in HF versus C and HP at 25 weeks (P.05). HF decreased hepatic cholesterol content compared to HP and C at 25 weeks. HF and HP increased 3-hydroxy-3-methylglutaryl-CoA reductase mRNA and decreased lecithin-cholesterol acyltransferase mRNA compared to C (P.05). In conclusion, re-matching rats to a HF but not HP diet attenuated the typical increase in Firmicutes:Bacteroidetes ratio associated with consumption of a high fat diet. Lower hepatic cholesterol with long-term HF diet intake may be related to alterations in gut microbiota and hepatic lipid metabolism.

Maternal gut microbiota and milk composition could modify offspring microbiota and therefore disease susceptibility. The effect of maternal high-protein (HP) or prebiotic diets on maternal milk composition and gut microbiota in rat dams and offspring was examined.Wistar rat dams were fed a control, HP (40% wt/wt), or high-prebiotic-fiber (21.6% wt/wt) (HF) diet throughout pregnancy and lactation. Pups were challenged with a high-fat/sucrose diet from 14.5 to 22.5 weeks of age. Dam milk was analyzed for fat, protein, and oligosaccharides (OS). Fecal microbiota was analyzed in dams at parturition and 2 weeks post-partum and in offspring at 5 and 22 weeks along with cecal digesta at termination.Maternal milk differed only in OS content, each diet group being distinguishable. HF1 and HP1 offspring had decreased plasma lipopolysaccharide compared with C1. Offspring sex, maternal diet, and time (5 weeks vs. 22 weeks of age) affected the microbial groups examined. Bifidobacteria was higher in HF dams and offspring.Increasing protein or fiber content in maternal diet during pregnancy and lactation modifies milk OS content and gut microbiota of dams which may influence establishment of gut microbiota in offspring.

Numerous studies have demonstrated the impact of functional fibers on gut microbiota and metabolic health, but some less well-studied fibers and/or fractions of foods known to be high in fiber still warrant examination. The aim of this study was to assess the effect of yellow pea-derived fractions varying in fiber and protein content on metabolic parameters and gut microbiota in diet-induced obese rats. We hypothesized that the yellow pea fiber (PF) fraction would improve glycemia and alter gut microbiota. Rats were randomized to 1 of 5 isoenergetic dietary treatments for 6 weeks: (1) control; (2) oligofructose (OFS); (3) yellow PF; (4) yellow pea flour (PFL); or (5) yellow pea starch (PS). Glycemia, plasma gut hormones, body composition, hepatic triglyceride content, gut microbiota, and messenger RNA expression of genes related to hepatic fat metabolism were examined. Pea flour attenuated weight gain compared with control, PF, and PS (P < .05). Pea flour, PS, and OFS had significantly lower final percent body fat compared with control. Oligofructose but not the pea fraction diets reduced food intake compared with control (P < .05). Pea fiber resulted in lower fasting glucose and glucose area under the curve compared with control. Changes in gut microbiota were fraction specific and included a decrease in Firmicutes (percent) for OFS, PF, and PFL compared with control (P < .05). The Firmicutes/Bacteroidetes ratio was reduced with OFS, PF, and PFL when compared with PS (P < .05). Taken together, this work suggests that yellow pea-derived fractions are able to distinctly modulate metabolic parameters and gut microbiota in obese rats.

Background: Intestinal microbiota are increasingly recognized as potential modifiers of whole-body energy metabolism. Previous research has described changes in bacterial composition in diabetes; this study examines whether these differences can be altered with lifestyle treatment. Methods: Six-week-old diabetic (db/db) and control littermates (db+) were randomized into sedentary or exercise training groups for 6 weeks (n=9-10/treatment). All animals consumed an identical, chow-based diet. Exercise consisted of low-intensity treadmill running (5d/week), and was ceased 48h prior to sacrifice. Cecal matter was collected from individual mice at sacrifice. Total bacterial DNA was extracted and quantified, and bacterial species were detected and profiled using qPCR and group specific primers. Genomic data is reported as the log transformed 16S rRNA copy number normalized for the amount of cecal matter analyzed. Results: Compared to db+ mice, db/db had higher Clostridium Difficile and lower Clostridium Perfring...

Diabetes is characterized by hyperphagia and increased absorption of nutrients from the small intestine coupled with inadequate insulin secretion. Ingestion of fermentable fiber by non-diabetic rats is associated with increased intestinal proglucagon mRNA and greater postprandial release of glucagon-like peptide (GLP-1). To determine if food intake and fiber fermentability had similar effects on intestinal proglucagon mRNA in diabetic rats, diets containing cellulose (CEL) or rhubarb (RH) were fed to streptozotocin-diabetic Sprague-Dawley rats (Sz-SD), Sz-SD pair-fed to non-diabetic SD controls, and BB diabetic rats (10/treatment) for 14d. Jejunal, ileal and colonic weights were significantly affected by food intake and ileal weight was greater in RH-fed rats. Ileal and colonic proglucagon mRNA abundance's were greater in CEL-fed vs. RH-fed rats regardless of food intake and opposite to that observed in non-diabetic rats (1). Diet did not affect intestinal glucose uptakes in vitro except for increased ileal uptake in pair-fed rats eating CEL vs. RH. Jejunal mRNA abundance's for glucose transporters SGLT-1 and GLUT2 were greater in ad lib-fed rats and in RH vs. CEL-fed rats. This study confirms reports that jejunal glucose transport capacity is positively correlated with food intake. Proglucagon gene expression in diabetic rats responds to fermentable fiber but differs from that determined in non-diabetic rats.