1. Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice
- Author
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Patrice Martin, Catherine Philippe, Gabriel Perlemuter, Francine Walker, Tiphaine Le Roy, Anne-Marie Cassard-Doulcier, Sylvie Rabot, Marta Llopis, Philippe Gérard, Aurélia Bruneau, Claudia Bevilacqua, Patricia Lepage, André Bado, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Génétique Animale et Biologie Intégrative (GABI), UFR de médecine, U773, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (Inserm), Cytokines, chimiokines et immunopathologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Faculté de médecine, Université Paris-Sud - Paris 11 (UP11), Hôpital Antoine Béclère, Service d'hépato-gastroentérologie, Assistance Publique - Hôpitaux de Paris, Science Committee Syndifrais/CNIEL, CNIEL (Centre National Interprofessionnel de l'Economie Laitiere) [S2234], Gerard, Philippe, ProdInra, Archive Ouverte, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), and AgroParisTech-Institut National de la Recherche Agronomique (INRA)
- Subjects
Blood Glucose ,Male ,[SDV]Life Sciences [q-bio] ,Gut flora ,Systemic inflammation ,Polymerase Chain Reaction ,Mice ,Colonic Microflora ,Cytokines ,Fatty Liver ,Real Time PCR ,Lipid Metabolism ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,RNA, Ribosomal, 16S ,cytokine ,0303 health sciences ,biology ,Microbiota ,Fatty liver ,Gastroenterology ,Intestines ,[SDV] Life Sciences [q-bio] ,RNA, Bacterial ,Liver ,Lipogenesis ,030211 gastroenterology & hepatology ,medicine.symptom ,medicine.medical_specialty ,digestive system ,03 medical and health sciences ,stéatose hépatique ,Internal medicine ,medicine ,Animals ,Triglycerides ,030304 developmental biology ,pcr en temps réel ,métabolisme lipidique ,nutritional and metabolic diseases ,Lipid metabolism ,Fatty Acids, Volatile ,medicine.disease ,biology.organism_classification ,Dietary Fats ,Obesity ,Mice, Inbred C57BL ,Transplantation ,Endocrinology ,microflore digestive ,Metabolic syndrome - Abstract
Objective: Non-alcoholic fatty liver disease (NAFLD) is prevalent among obese people and is considered the hepatic manifestation of metabolic syndrome. However, not all obese individuals develop NAFLD. Our objective was to demonstrate the role of the gut microbiota in NAFLD development using transplantation experiments in mice. [br/] Design: Two donor C57BL/6J mice were selected on the basis of their responses to a high-fat diet (HFD). Although both mice displayed similar body weight gain, one mouse, called the responder', developed hyperglycaemia and had a high plasma concentration of pro-inflammatory cytokines. The other, called a non-responder', was normoglycaemic and had a lower level of systemic inflammation. Germ-free mice were colonised with intestinal microbiota from either the responder or the non-responder and then fed the same HFD. [br/] Results: Mice that received microbiota from different donors developed comparable obesity on the HFD. The responder-receiver (RR) group developed fasting hyperglycaemia and insulinaemia, whereas the non-responder-receiver (NRR) group remained normoglycaemic. In contrast to NRR mice, RR mice developed hepatic macrovesicular steatosis, which was confirmed by a higher liver concentration of triglycerides and increased expression of genes involved in de-novo lipogenesis. Pyrosequencing of the 16S ribosomal RNA genes revealed that RR and NRR mice had distinct gut microbiota including differences at the phylum, genera and species levels. [br/] Conclusions: Differences in microbiota composition can determine response to a HFD in mice. These results further demonstrate that the gut microbiota contributes to the development of NAFLD independently of obesity.
- Published
- 2013