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Germ‐free C57BL/6J mice are resistant to high‐fat‐diet‐induced insulin resistance and have altered cholesterol metabolism
Abstract
Recent studies showed that germ‐free (GF) mice are resistant to obesity when consuming a high‐fat, high‐carbohydrate Western diet. However, it remains unclear what mechanisms are involved in the antiobesity phenotype and whether GF mice develop insulin resistance and dyslipidemia with high‐fat (HF) feeding. In the present study, we compared the metabolic consequences of HF feeding on GF and conventional (conv) C57BL/6J mice. GFmice consumed fewer calories, excreted more fecal lipids, and weighed significantly less than conv mice. GF/HF animals also showed enhanced insulin sensitivity with improved glucose tolerance, reduced fasting and nonfasting insuline‐mia, and increased phospho‐Akt (Ser‐473) in adipose tissue. In association with enhanced insulin sensitivity, GF/HF mice had reduced plasma TNF‐α and total serum amyloid A concentrations. Reduced hypercholes‐terolemia, a moderate accretion of hepatic cholesterol, and an increase in fecal cholesterol excretion suggest an altered cholesterol metabolism in GF/HF mice. Pronounced nucleus SREBP2 proteins and up‐regulation of cholesterol biosynthesis genes indicate that enhanced cholesterol biosynthesis contributed to the cholesterol homeostasis in GF/HF mice. Our results demonstrate that fewer calorie consumption and increased lipid excretion contributed to the obesity‐resistant phenotype of GF/HF mice and reveal that insulin sensitivity and cholesterol metabolism are metabolic targets influenced by the gut microbiota.— Rabot, S., Membrez, M., Bruneau, A., Gerard, P., Harach, T., Moser, M., Raymond, F., Mansourian, R., Chou. C. J. Germ‐free C57BL/6J mice are resistant to high‐fat‐diet‐induced insulin resistance and have altered cholesterol metabolism. FASEB J. 24, 4948–4959 (2010). www.fasebj.org
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“germ-free mice are resistant to the obesogenic effects of high-fat diets243”
From Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management (2023) · cites this paper as [243]
In the citing paper
“Germ-free (GF) mice are protected from the metabolic consequences of high-fat diets, suggesting that gut microbes may be important mediators of lipid-induced metabolic dysfunction (28).”
From The gut microbiota at the intersection of diet and human health (2018) · cites this paper as [28]
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“The gut microbiota has been shown to affect lipid metabolism and lipid levels in blood and tissues, both in mice and humans.”
From Dietary lipids, gut microbiota and lipid metabolism (2019) · cites this paper as [31]
In the citing paper
“In contrast, circulating triglycerides, HDL, and total cholesterol levels are increased by the gut microbiota in mice on a high-fat diet [31].”
From Dietary lipids, gut microbiota and lipid metabolism (2019) · cites this paper as [31]
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Impact du microbiome intestinal sur la cholestérolémie : concepts et applications
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Metadata
- Authors
- Rabot, S., Membrez, M., Bruneau, A., Gérard, P., Harach, T., Moser, M., Raymond, F., Mansourian, R., & Chou, C. J.
- Affiliations
- Microbiologie de l’alimentation au service de la santé (FR)
- Department of Nutrition and Health Nestlé Research Center Lausanne Switzerland
- Nestlé (Switzerland) (CH)
- Department of Bioanalytical Science Nestlé Research Center Lausanne Switzerland
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2010-08-19
- Volume
- 24
- Issue
- 12
- Pages
- 4948-4959
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2088697466
- Cited by
- 610
- References
- 41
- Citations by year
- 2026: 9 · 2025: 19 · 2024: 34 · 2023: 43 · 2022: 50 · 2021: 64 · 2020: 75 · 2019: 49 · 2018: 42 · 2017: 40 · 2016: 39 · 2015: 44 · 2014: 24 · 2013: 33 · 2012: 22
- FWCI
- 10.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- germ-free mice, gut microbiota, high-fat diet, insulin resistance, cholesterol metabolism, hypercholesterolemia, obesity resistance, glucose tolerance, TNF-α, serum amyloid A, SREBP2, cholesterol biosynthesis, liver cholesterol, fecal cholesterol excretion, C57BL/6J mice
- MeSH terms
- Animals, Body Weight, Cholesterol, Dietary Fats, Germ-Free Life, Glucose Tolerance Test, Glycogen, Insulin Resistance, Lipids, Liver, Male, Mice, Inbred C57BL, Obesity, Blotting, Western, Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Mice
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