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Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice.

Everard A, Lazarevic V, Derrien M, Girard M, Muccioli GG, Muccioli GM, Neyrinck AM, Possemiers S, Van Holle A, François P, de Vos WM, Delzenne NM, Schrenzel J, Cani PD - Diabetes (2011)

Bottom Line: Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models.In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation.We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice.

View Article: PubMed Central - PubMed

Affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.

ABSTRACT

Objective: To investigate deep and comprehensive analysis of gut microbial communities and biological parameters after prebiotic administration in obese and diabetic mice.

Research design and methods: Genetic (ob/ob) or diet-induced obese and diabetic mice were chronically fed with prebiotic-enriched diet or with a control diet. Extensive gut microbiota analyses, including quantitative PCR, pyrosequencing of the 16S rRNA, and phylogenetic microarrays, were performed in ob/ob mice. The impact of gut microbiota modulation on leptin sensitivity was investigated in diet-induced leptin-resistant mice. Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models.

Results: In ob/ob mice, prebiotic feeding decreased Firmicutes and increased Bacteroidetes phyla, but also changed 102 distinct taxa, 16 of which displayed a >10-fold change in abundance. In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation. In high fat-fed mice, prebiotic treatment improved leptin sensitivity as well as metabolic parameters.

Conclusions: We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice. By profiling the gut microbiota, we identified a catalog of putative bacterial targets that may affect host metabolism in obesity and diabetes.

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Prebiotic-induced changes in gut microbiota are associated with improved leptin sensitivity and glucose homeostasis in diet-induced obese and diabetic mice. A: Plasma glucose profile after 2 g/kg glucose oral challenge in freely moving mice in the HF (■) and the HF-Pre (□) mice. B: Body weight gain. C: Lean body mass measured by nuclear magnetic resonance. D: Adiposity index, corresponding to the sum of the subcutaneous, the visceral, and the epididymal adipose depot weights. E: Colon proglucagon mRNA expression. F: Portal plasma GLP-1 level content. Mean ± SEM. n = 8 (HF) and 9 (HF-Pre). *P < 0.05; #P = 0.08, determined by a two-tailed Student t test. G: Body weight changes 2 days after twice-daily intraperitoneal leptin (0.375 mg/kg) in the HF (HF-L) and the HF-Pre mice (HF-Pre-L). Data from each group were normalized to their own paired saline control. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a two-tailed Student t test. H: Food intake 24 h after two doses of intraperitoneal leptin (Lep) (0.375 mg/kg). Data from each group are compared with their own paired saline control (Sal) vs. leptin. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a paired Student t test. I: Adipose tissue acetyl-CoA carboxylase (ACC) mRNA expression 6 h after intraperitoneal leptin (1 mg/kg) or saline in the HF (HF-L) and the HF-Pre mice (HF-Pre-L). Data from each group were normalized to their own saline control. Mean ± SEM. Saline, n = 4 mice/group; leptin, n = 6 mice/group. *P < 0.05, determined by a two-tailed Student t test.
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Figure 5: Prebiotic-induced changes in gut microbiota are associated with improved leptin sensitivity and glucose homeostasis in diet-induced obese and diabetic mice. A: Plasma glucose profile after 2 g/kg glucose oral challenge in freely moving mice in the HF (■) and the HF-Pre (□) mice. B: Body weight gain. C: Lean body mass measured by nuclear magnetic resonance. D: Adiposity index, corresponding to the sum of the subcutaneous, the visceral, and the epididymal adipose depot weights. E: Colon proglucagon mRNA expression. F: Portal plasma GLP-1 level content. Mean ± SEM. n = 8 (HF) and 9 (HF-Pre). *P < 0.05; #P = 0.08, determined by a two-tailed Student t test. G: Body weight changes 2 days after twice-daily intraperitoneal leptin (0.375 mg/kg) in the HF (HF-L) and the HF-Pre mice (HF-Pre-L). Data from each group were normalized to their own paired saline control. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a two-tailed Student t test. H: Food intake 24 h after two doses of intraperitoneal leptin (Lep) (0.375 mg/kg). Data from each group are compared with their own paired saline control (Sal) vs. leptin. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a paired Student t test. I: Adipose tissue acetyl-CoA carboxylase (ACC) mRNA expression 6 h after intraperitoneal leptin (1 mg/kg) or saline in the HF (HF-L) and the HF-Pre mice (HF-Pre-L). Data from each group were normalized to their own saline control. Mean ± SEM. Saline, n = 4 mice/group; leptin, n = 6 mice/group. *P < 0.05, determined by a two-tailed Student t test.

Mentions: We further investigated a dietary obesity model to identify the impact of prebiotic feeding when leptin signaling becomes compromised. Here we found that prebiotic feeding markedly improved glucose tolerance, reduced body weight and fat mass, and increased muscle mass (Fig. 5A–D). Mean food intake (kcal/mice/day) (HF 20.9 ± 0.6, HF-Pre 19.6 ± 0.3) was not significantly affected.


Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice.

Everard A, Lazarevic V, Derrien M, Girard M, Muccioli GG, Muccioli GM, Neyrinck AM, Possemiers S, Van Holle A, François P, de Vos WM, Delzenne NM, Schrenzel J, Cani PD - Diabetes (2011)

Prebiotic-induced changes in gut microbiota are associated with improved leptin sensitivity and glucose homeostasis in diet-induced obese and diabetic mice. A: Plasma glucose profile after 2 g/kg glucose oral challenge in freely moving mice in the HF (■) and the HF-Pre (□) mice. B: Body weight gain. C: Lean body mass measured by nuclear magnetic resonance. D: Adiposity index, corresponding to the sum of the subcutaneous, the visceral, and the epididymal adipose depot weights. E: Colon proglucagon mRNA expression. F: Portal plasma GLP-1 level content. Mean ± SEM. n = 8 (HF) and 9 (HF-Pre). *P < 0.05; #P = 0.08, determined by a two-tailed Student t test. G: Body weight changes 2 days after twice-daily intraperitoneal leptin (0.375 mg/kg) in the HF (HF-L) and the HF-Pre mice (HF-Pre-L). Data from each group were normalized to their own paired saline control. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a two-tailed Student t test. H: Food intake 24 h after two doses of intraperitoneal leptin (Lep) (0.375 mg/kg). Data from each group are compared with their own paired saline control (Sal) vs. leptin. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a paired Student t test. I: Adipose tissue acetyl-CoA carboxylase (ACC) mRNA expression 6 h after intraperitoneal leptin (1 mg/kg) or saline in the HF (HF-L) and the HF-Pre mice (HF-Pre-L). Data from each group were normalized to their own saline control. Mean ± SEM. Saline, n = 4 mice/group; leptin, n = 6 mice/group. *P < 0.05, determined by a two-tailed Student t test.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
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Figure 5: Prebiotic-induced changes in gut microbiota are associated with improved leptin sensitivity and glucose homeostasis in diet-induced obese and diabetic mice. A: Plasma glucose profile after 2 g/kg glucose oral challenge in freely moving mice in the HF (■) and the HF-Pre (□) mice. B: Body weight gain. C: Lean body mass measured by nuclear magnetic resonance. D: Adiposity index, corresponding to the sum of the subcutaneous, the visceral, and the epididymal adipose depot weights. E: Colon proglucagon mRNA expression. F: Portal plasma GLP-1 level content. Mean ± SEM. n = 8 (HF) and 9 (HF-Pre). *P < 0.05; #P = 0.08, determined by a two-tailed Student t test. G: Body weight changes 2 days after twice-daily intraperitoneal leptin (0.375 mg/kg) in the HF (HF-L) and the HF-Pre mice (HF-Pre-L). Data from each group were normalized to their own paired saline control. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a two-tailed Student t test. H: Food intake 24 h after two doses of intraperitoneal leptin (Lep) (0.375 mg/kg). Data from each group are compared with their own paired saline control (Sal) vs. leptin. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a paired Student t test. I: Adipose tissue acetyl-CoA carboxylase (ACC) mRNA expression 6 h after intraperitoneal leptin (1 mg/kg) or saline in the HF (HF-L) and the HF-Pre mice (HF-Pre-L). Data from each group were normalized to their own saline control. Mean ± SEM. Saline, n = 4 mice/group; leptin, n = 6 mice/group. *P < 0.05, determined by a two-tailed Student t test.
Mentions: We further investigated a dietary obesity model to identify the impact of prebiotic feeding when leptin signaling becomes compromised. Here we found that prebiotic feeding markedly improved glucose tolerance, reduced body weight and fat mass, and increased muscle mass (Fig. 5A–D). Mean food intake (kcal/mice/day) (HF 20.9 ± 0.6, HF-Pre 19.6 ± 0.3) was not significantly affected.

Bottom Line: Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models.In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation.We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice.

View Article: PubMed Central - PubMed

Affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.

ABSTRACT

Objective: To investigate deep and comprehensive analysis of gut microbial communities and biological parameters after prebiotic administration in obese and diabetic mice.

Research design and methods: Genetic (ob/ob) or diet-induced obese and diabetic mice were chronically fed with prebiotic-enriched diet or with a control diet. Extensive gut microbiota analyses, including quantitative PCR, pyrosequencing of the 16S rRNA, and phylogenetic microarrays, were performed in ob/ob mice. The impact of gut microbiota modulation on leptin sensitivity was investigated in diet-induced leptin-resistant mice. Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models.

Results: In ob/ob mice, prebiotic feeding decreased Firmicutes and increased Bacteroidetes phyla, but also changed 102 distinct taxa, 16 of which displayed a >10-fold change in abundance. In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation. In high fat-fed mice, prebiotic treatment improved leptin sensitivity as well as metabolic parameters.

Conclusions: We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice. By profiling the gut microbiota, we identified a catalog of putative bacterial targets that may affect host metabolism in obesity and diabetes.

Show MeSH
Related in: MedlinePlus