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Germ‐free C57BL/6J mice are resistant to high‐fat‐diet‐induced insulin resistance and have altered cholesterol metabolism

2010; Wiley; Volume: 24; Issue: 12 Linguagem: Inglês

10.1096/fj.10.164921

1530-6860

Sylvie Rabot, Mathieu Membrez, Aurélia Bruneau, Philippe Gérard, Taoufiq Harach, Mireille Moser, Frédéric Raymond, Robert Mansourian, Chieh Jason Chou,

Adipokines, Inflammation, and Metabolic Diseases

The FASEB JournalVolume 24, Issue 12 p. 4948-4959 Research CommunicationFree to Read Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism Sylvie Rabot, Sylvie Rabot Institut National de la Recherche Agronomique, UMR1319 Micalis, Jouy-en-Josas, France These authors contributed equally to this work.Search for more papers by this authorMathieu Membrez, Mathieu Membrez Department of Nutrition and Health, Nestlé Research Center, Lausanne, Switzerland These authors contributed equally to this work.Search for more papers by this authorAurélia Bruneau, Aurélia Bruneau Institut National de la Recherche Agronomique, UMR1319 Micalis, Jouy-en-Josas, FranceSearch for more papers by this authorPhilippe Gérard, Philippe Gérard Institut National de la Recherche Agronomique, UMR1319 Micalis, Jouy-en-Josas, FranceSearch for more papers by this authorTaoufiq Harach, Taoufiq Harach Department of Nutrition and Health, Nestlé Research Center, Lausanne, SwitzerlandSearch for more papers by this authorMireille Moser, Mireille Moser Department of Bioanalytical Science, Nestlé Research Center, Lausanne, SwitzerlandSearch for more papers by this authorFrederic Raymond, Frederic Raymond Department of Bioanalytical Science, Nestlé Research Center, Lausanne, SwitzerlandSearch for more papers by this authorRobert Mansourian, Robert Mansourian Department of Bioanalytical Science, Nestlé Research Center, Lausanne, SwitzerlandSearch for more papers by this authorChieh J. Chou, Corresponding Author Chieh J. Chou chieh-jason.chou@rdls.nestle.com Department of Nutrition and Health, Nestlé Research Center, Lausanne, Switzerland Correspondence: Nestlé Research Center, Rte. du Jorat 57, Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland. E-mail: chieh-jason.chou@rdls.nestle.comSearch for more papers by this author Sylvie Rabot, Sylvie Rabot Institut National de la Recherche Agronomique, UMR1319 Micalis, Jouy-en-Josas, France These authors contributed equally to this work.Search for more papers by this authorMathieu Membrez, Mathieu Membrez Department of Nutrition and Health, Nestlé Research Center, Lausanne, Switzerland These authors contributed equally to this work.Search for more papers by this authorAurélia Bruneau, Aurélia Bruneau Institut National de la Recherche Agronomique, UMR1319 Micalis, Jouy-en-Josas, FranceSearch for more papers by this authorPhilippe Gérard, Philippe Gérard Institut National de la Recherche Agronomique, UMR1319 Micalis, Jouy-en-Josas, FranceSearch for more papers by this authorTaoufiq Harach, Taoufiq Harach Department of Nutrition and Health, Nestlé Research Center, Lausanne, SwitzerlandSearch for more papers by this authorMireille Moser, Mireille Moser Department of Bioanalytical Science, Nestlé Research Center, Lausanne, SwitzerlandSearch for more papers by this authorFrederic Raymond, Frederic Raymond Department of Bioanalytical Science, Nestlé Research Center, Lausanne, SwitzerlandSearch for more papers by this authorRobert Mansourian, Robert Mansourian Department of Bioanalytical Science, Nestlé Research Center, Lausanne, SwitzerlandSearch for more papers by this authorChieh J. Chou, Corresponding Author Chieh J. Chou chieh-jason.chou@rdls.nestle.com Department of Nutrition and Health, Nestlé Research Center, Lausanne, Switzerland Correspondence: Nestlé Research Center, Rte. du Jorat 57, Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland. E-mail: chieh-jason.chou@rdls.nestle.comSearch for more papers by this author First published: 19 August 2010 https://doi.org/10.1096/fj.10.164921Citations: 43 This article includes supplemental data. Please visit http://www.fasebj.org to obtain this information. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat 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 Citing Literature Supporting Information Filename Description fsb2fj10164921-sup-0001.docPDF document, 377.5 KB Supplementary Material Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume24, Issue12December 2010Pages 4948-4959 RelatedInformation