Protein quality and the protein to carbohydrate ratio within a high fat diet influences energy balance and the gut microbiota in C57BL/6J mice.
ABSTRACT: Macronutrient quality and composition are important determinants of energy balance and the gut microbiota. Here, we investigated how changes to protein quality (casein versus whey protein isolate; WPI) and the protein to carbohydrate (P/C) ratio within a high fat diet (HFD) impacts on these parameters. Mice were fed a low fat diet (10% kJ) or a high fat diet (HFD; 45% kJ) for 21 weeks with either casein (20% kJ, HFD) or WPI at 20%, 30% or 40% kJ. In comparison to casein, WPI at a similar energy content normalised energy intake, increased lean mass and caused a trend towards a reduction in fat mass (P = 0.08), but the protein challenge did not alter oxygen consumption or locomotor activity. WPI reduced HFD-induced plasma leptin and liver triacylglycerol, and partially attenuated the reduction in adipose FASN mRNA in HFD-fed mice. High throughput sequence-based analysis of faecal microbial populations revealed microbiota in the HFD-20% WPI group clustering closely with HFD controls, although WPI specifically increased Lactobacillaceae/Lactobacillus and decreased Clostridiaceae/Clostridium in HFD-fed mice. There was no effect of increasing the P/C ratio on energy intake, but the highest ratio reduced HFD-induced weight gain, fat mass and plasma triacylglycerol, non-esterified fatty acids, glucose and leptin levels, while it increased lean mass and oxygen consumption. Similar effects were observed on adipose mRNA expression, where the highest ratio reduced HFD-associated expression of UCP-2, TNF? and CD68 and increased the diet-associated expression of ?3-AR, LPL, IR, IRS-1 and GLUT4. The P/C ratio also impacted on gut microbiota, with populations in the 30/40% WPI groups clustering together and away from the 20% WPI group. Taken together, our data show that increasing the P/C ratio has a dramatic effect on energy balance and the composition of gut microbiota, which is distinct from that caused by changes to protein quality.
Project description:Bovine whey protein has been demonstrated to exert a positive effect on energy balance, lipid metabolism, and nutrient absorption. Additionally, it affects gut microbiota configuration. Thus, whey protein is considered as good dietary candidate to prevent or ameliorate metabolic diseases, such as obesity. However, the relationship that links energy balance, metabolism, and intestinal microbial population mediated by whey protein intake remains poorly understood. In this study, we investigated the beneficial effects attributed to whey protein in the context of high-fat diet (HFD) in mice at two different ages, with short or longer durations of whey protein supplementation. Here, a 5-week dietary intervention with HFD in combination with either whey protein isolate (WPI) or the control nonwhey milk protein casein (CAS) was performed using 5-week or 10-week-old C57BL/6J mice. Notably, the younger mice had no prior history of ingestion of WPI, while older mice did. 5-week-old HFD-WPI-fed mice showed a decrease in weight gain and changes in the expression of genes within the epidydimal white adipose tissue including those encoding leptin, inflammatory marker CD68, fasting-induced adipose factor FIAF and enzymes involved in fatty acids catabolism, relative to HFD-CAS-fed mice. Differences in ?-diversity and higher proportions of Lactobacillus murinus, and related functions, were evident within the gut microbiota of HFD-WPI mice. However, none of these changes were observed in mice that started the HFD dietary intervention at 10-weeks-old, with an extended period of WPI supplementation. These results suggest that the effect of whey protein on mouse body weight, adipose tissue, and intestinal parameters depends on diet duration and stage of life during which the diet is provided. In some instances, WPI influences gut microbiota composition and functional potential, which might orchestrate observed metabolic and physiological modifications.
Project description:Obesity and related disorders, which are increasing in adults worldwide, are closely linked to childhood diet and are associated with chronic inflammation. Rice endosperm protein (REP) intake during adulthood has been reported to improve lipid metabolism and suppress the progression of diabetic kidney disease in animal models. However, the effects of REP intake during childhood on adulthood health are unclear. Therefore, we used a mouse model to experimentally investigate the preconditioning effects of REP intake during childhood on the development of obesity and related disorders in adulthood. Male C57BL/6J mice were pair-fed a normal-fat diet containing casein or REP during the juvenile period and then a high-fat diet (HFD) containing casein or REP during adulthood. Mice fed REP during the juvenile period showed better body weight, blood pressure, serum lipid profiles, lipopolysaccharide (LPS)-binding protein levels, and glucose tolerance in adulthood than those fed casein during the juvenile period. HFD-induced renal tubulo-glomerular alterations and hepatic microvesicular steatosis were less evident in REP-fed mice than in casein-fed ones. REP intake during the juvenile period improved HFD-induced dysbiosis (i.e., Escherichia genus proliferation and reduced gut microbiota diversity), thereby suppressing endotoxin-related chronic inflammation. Indeed, REP-derived peptides showed antibacterial activity against Escherichia coli, a major producer of LPS. In conclusion, REP supplementation during the juvenile period may regulate the gut microbiota and thus suppress the development of obesity and related disorders in adulthood in mice.
Project description:Consumption of dietary protein at recommended levels is considered a potential strategy to promote satiety and weight management, but how protein from different dietary sources effect the obesity development, lipid metabolism, and gut microbiota is not known. This study focused on the effects of beef, casein, and soy protein diet on lipid metabolism, triglycerides accumulation, and microbial diversity in colon of C57BL/6J mice, which were given either low-fat diets (LFD, 12% Kcal) or high-fat diets (HFD, 60% Kcal) for 12 weeks. Body and liver weight increased significantly in mice fed a beef protein HFD (HFB), whereas reduced cumulative energy intake was seen in a soy protein HFD (HFS) group. HFB-fed mice showed signs of impaired glucose metabolism and insulin resistance along with a significant elevation in the concentration of triglycerides, LDL-cholesterol, total cholesterol, IL1?, TNF-?, IL-6, and leptin in serum. HFB also enhanced lipid accumulation in liver with increased activity of genes important for lipogenesis and hepatic cholesterol metabolism. A 16S rRNA gene sequencing indicated that HFD, regardless of proteins, significantly enhanced the ratio of Firmicutes to Bacteroidetes in colonic microbiota. However, HFB not only reduced the abundance of Akkermansia, compared with LFD independent of proteins, but also decreased the abundance of butyrate-producing bacteria such as Anaerotruncus, Butyricicoccus, and Lactobacillus (P < 0.05) compared with HFS and HFC. In conclusion, consumption of HFB does not only affect the gut microbiota composition but also increases the problems related to metabolic syndromes like dyslipidemia, hypercholesterolemia, and triglycerides accumulation in liver, which lead to systemic inflammation and its associated comorbidities, for example, impaired glucose metabolism and insulin resistance.
Project description:Obesity is closely associated with various metabolic disorders, including leptin resistance, which is characterized by high circulating leptin levels. Probiotics can decrease circulating leptin levels by alteration of the gut microbiota. Thus, they may have anti-obesogenic effects. In this study, the effects of administration of a probiotic bacterium, Lactobacillus rhamnosus GG (LGG), on gut microbiota and modulation of leptin resistance were evaluated in mice. Male Balb/C mice aged 7 weeks were fed either a normal diet (ND), high-fat diet (HFD), HFD supplemented with low-dose LGG (108 CFU/mouse/day), or HFD supplemented with high-dose LGG (1010 CFU/mouse/day) for 10 weeks. Significantly increased body weight, epididymal fat weight, and decreased leptin responsiveness to exogenous leptin treatment and ratio of villus height to crypt depth were observed in the HFD-fed mice compared to the ND-fed mice. Moreover, a remarkable increase in the proportion of Proteobacteria and ratio of Firmicutes/Bacteroidetes in the fecal microbiota were also observed in the HFD-fed mice. Supplementation of HFD with high-dose LGG restored exogenous leptin responsiveness, increased the ratio of villus height to crypt depth, and decreased the proportion of Proteobacteria in fecal microbiota. These findings suggest that LGG supplementation might alleviate leptin resistance caused by an HFD through the improvement of the digestive health of the host.
Project description:Diet-induced obesity is associated with changes in the gut microbiota and low-grade inflammation. Oligofructose was reported to ameliorate high fat diet-induced metabolic disorders in mice by restoring the number of intestinal bifidobacteria. However, this has not been experimentally demonstrated.We fed conventional mice, germfree mice, mice associated with a simplified human gut microbiota composed of eight bacterial species including Bifidobacterium longum (SIHUMI), and mice associated with SIHUMI without B. longum a low fat diet (LFD), a high fat diet (HFD), or a HFD containing 10% oligofructose (HFD + OFS) for five weeks. We assessed body composition, bacterial cell numbers and metabolites, markers of inflammation, and gut permeability. Conventional mice fed HFD or HFD + OFS did not differ in body weight gain and glucose tolerance. The gnotobiotic mouse groups fed LFD or HFD + OFS gained less body weight and body fat, and displayed an improved glucose tolerance compared with mice fed HFD. These differences were not affected by the presence of B. longum. Mice fed HFD showed no signs of inflammation or increased intestinal permeability.The ability of oligofructose to reduce obesity and to improve glucose tolerance in gnotobiotic mice fed HFD was independent of the presence of B. longum.
Project description:Asperlin is a marine-derived, natural product with antifungal, anti-inflammatory and anti-atherosclerotic activities. In the present study, we showed that asperlin effectively prevented the development of obesity in high-fat diet (HFD)-fed mice. Oral administration of asperlin for 12 weeks significantly suppressed HFD-induced body weight gain and fat deposition without inhibiting food intake. Hyperlipidemia and liver steatosis were also substantially ameliorated. A respiratory metabolism monitor showed that asperlin efficiently increased energy expenditure and enhanced thermogenic gene expression in adipose tissue. Accordingly, asperlin-treated mice showed higher body temperature and were more tolerant of cold stress. Meanwhile, asperlin also increased the diversity and shifted the structure of gut microbiota. Oral administration of asperlin markedly increased the relative abundance of Bacteroidetes, leading to a higher Bacteroidetes-to-Fimicutes ratio. The HFD-induced abnormalities at both phylum and genus levels were all remarkably recovered by asperlin. These results demonstrated that asperlin is effective in preventing HFD-induced obesity and modulating gut microbiota. Its anti-obesity properties may be attributed to its effect on promoting energy expenditure.
Project description:Diet and exercise underpin the risk of obesity-related metabolic disease. Diet alters the gut microbiota, which contributes to aspects of metabolic disease during obesity. Repeated exercise provides metabolic benefits during obesity. We assessed whether exercise could oppose changes in the taxonomic and predicted metagenomic characteristics of the gut microbiota during diet-induced obesity. We hypothesized that high-intensity interval training (HIIT) would counteract high-fat diet (HFD)-induced changes in the microbiota without altering obesity in mice. Compared with chow-fed mice, an obesity-causing HFD decreased the Bacteroidetes-to-Firmicutes ratio and decreased the genetic capacity in the fecal microbiota for metabolic pathways such as the tricarboxylic acid (TCA) cycle. After HFD-induced obesity was established, a subset of mice were HIIT for 6 wk, which increased host aerobic capacity but did not alter body or adipose tissue mass. The effects of exercise training on the microbiota were gut segment dependent and more extensive in the distal gut. HIIT increased the alpha diversity and Bacteroidetes/Firmicutes ratio of the distal gut and fecal microbiota during diet-induced obesity. Exercise training increased the predicted genetic capacity related to the TCA cycle among other aspects of metabolism. Strikingly, the same microbial metabolism indexes that were increased by exercise were all decreased in HFD-fed vs. chow diet-fed mice. Therefore, exercise training directly opposed some of the obesity-related changes in gut microbiota, including lower metagenomic indexes of metabolism. Some host and microbial pathways appeared similarly affected by exercise. These exercise- and diet-induced microbiota interactions can be captured in feces.
Project description:Background:Obesity is a severe public health threat worldwide. Emerging evidence suggests that gut microbiota dysbiosis is closely associated with obesity and its related metabolic complications. The aim of the present study is to investigate the effects of polysaccharide extracted from WuGuChong (PEW) on high-fat diet (HFD)-induced obesity, and the potential mechanisms involving modulation of the gut microbiota composition. Methods:Mice were fed a normal chow diet and a high-fat diet with or without PEW (300?mg/kg/day) by oral gavage for 8?weeks. Body weight, obesity-related metabolic disorders, and gut microbiota were examined at the end of the experiment. Results:PEW supplementation reduces body weight, adipose hypertrophy, liver steatosis, insulin resistance and systemic inflammation in HFD-fed mice, as well as maintains intestinal epithelium integrity. High-throughput 16S rRNA analysis demonstrates that PEW supplementation alters the composition of gut microbiota. The Firmicutes to Bacteroidetes ratio and the relative abundance of Proteobacteria are increased in HFD-fed mice, which are reversed by PEW supplementation to approximately the control levels. Conclusions:Our results suggest that PEW may be used as a bioactive ingredient to prevent obesity and its related metabolic disorders by modulating the composition of gut microbiota.
Project description:<h4>Background & aims</h4>While it is widely accepted that obesity is associated with low-grade systemic inflammation, the molecular origin of the inflammation remains unknown. Here, we investigated the effect of endotoxin-induced inflammation via TLR4 signaling pathway at both systemic and intestinal levels in response to a high-fat diet.<h4>Methods</h4>C57BL/6J and TLR4-deficient C57BL/10ScNJ mice were maintained on a low-fat (10 kcal % fat) diet (LFD) or a high-fat (60 kcal % fat) diet (HFD) for 8 weeks.<h4>Results</h4>HFD induced macrophage infiltration and inflammation in the adipose tissue, as well as an increase in the circulating proinflammatory cytokines. HFD increased both plasma and fecal endotoxin levels and resulted in dysregulation of the gut microbiota by increasing the Firmicutes to Bacteriodetes ratio. HFD induced the growth of Enterobecteriaceae and the production of endotoxin in vitro. Furthermore, HFD induced colonic inflammation, including the increased expression of proinflammatory cytokines, the induction of Toll-like receptor 4 (TLR4), iNOS, COX-2, and the activation of NF-?B in the colon. HFD reduced the expression of tight junction-associated proteins claudin-1 and occludin in the colon. HFD mice demonstrated higher levels of Akt and FOXO3 phosphorylation in the colon compared to the LFD mice. While the body weight of HFD-fed mice was significantly increased in both TLR4-deficient and wild type mice, the epididymal fat weight and plasma endotoxin level of HFD-fed TLR4-deficient mice were 69% and 18% of HFD-fed wild type mice, respectively. Furthermore, HFD did not increase the proinflammatory cytokine levels in TLR4-deficient mice.<h4>Conclusions</h4>HFD induces inflammation by increasing endotoxin levels in the intestinal lumen as well as in the plasma by altering the gut microbiota composition and increasing its intestinal permeability through the induction of TLR4, thereby accelerating obesity.
Project description:Increased consumption of energy-rich foods is a key factor in overweight, obesity, and associated metabolic disorders. This would be, at least in part, related to microbiota disturbance. In rodent models of obesity, microbiota disruption has been associated with alteration of the intestinal barrier, endotoxemia, inflammation grade, and insulin sensitivity. The aim of the present study was to assess the effects of a high-fat diet (HFD), fed at two energetic levels, on microbiota, intestinal barrier, and inflammatory and metabolic parameters in dogs. A HFD (33% fat as fed, 4,830 kcal/kg) was given to 24 healthy Beagle dogs at 100% (HF-100; n = 8) and at 150% (HF-150; n = 16) of their maintenance energy requirements for 8 weeks. Analysis of similarity revealed a significant difference in gut microbiota ?-diversity following the diet compared to week 0 in both groups while ?-diversity was lower only in the HF-150 group. Firmicutes/Bacteroidetes ratio was higher in the HF-150 group compared to the HF-100 group at weeks 2 and 8. A reduction in insulin sensitivity was observed over time in the HF150 group. Neither endotoxemia nor inflammation was observed in either group, did not find supporting data for the hypothesis that the microbiota is involved in the decline of insulin sensitivity through metabolic endotoxemia and low-grade inflammation. Colonic permeability was increased at week 4 in both groups and returned to initial levels at week 8, and was associated with modifications to the expression of genes involved in colonic barrier function. The increase in intestinal permeability may have been caused by the altered intestinal microbiota and increased expression of genes encoding tight junction proteins might indicate a compensatory mechanism to restore normal permeability. Although simultaneous changes to the microbiota, barrier permeability, inflammatory, and metabolic status have not been observed, such a causal link cannot be excluded in dogs overfed on a HFD. Further studies are necessary to better understand the link between HFD, intestinal microbiota and the host.