ECE2019 Poster Presentations Diabetes, Obesity and Metabolism 3 (112 abstracts)
Transgenic production of endogenous n-3 PUFA levels compared to fish oil intake differentially improve obesity-related metabolic disorders: role of the gut microbiota
Mélanie Le Barz 1, , Noëmie Daniel 2, , Thibault V Varin 2, , Patricia Mitchell 2, , Geneviève Pilon 2, , Josée Gauthier 4 , Carole Garofalo 5 , Jing X Kang 6 , Denis Roy 3 , Christian Jobin 4 , Emile Lévy 5, & André Marette 2,
1INSERM U1060, INRA U1235, Laboratoire CarMeN, Lyon University, Université Claude Bernard Lyon 1, Lyon, France; 2Department of Medicine, Cardiology Axis of the Québec Heart and Lung Institute Research Centre, Quebec, Canada; 3Institute of Nutrition and Functional Foods, Laval University, Quebec, Canada; 4Department of Infectious Diseases and Pathology, and Department of Anatomy and Cell Physiology, University of Florida College of Medecine, Florida, USA; 5Research Centre, Sainte-Justine Hospital, Montréal, Canada. 6Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, USA; 7Department of Nutrition, University of Montreal, Montréal, Canada.
Previous studies demonstrated that n-3 polyunsaturated fatty acids (PUFA) reduce insulin resistance and non-alcoholic fatty liver disease (NAFLD). However, we previously reported that transgenic expression of the fat-1 n-3 desaturase, inducing the endogenous production of n-3 PUFA, improved insulin resistance but not hepatic steatosis in a mouse model of obesity. Thus, we compared the effects of increasing n-3 PUFA levels through oral or endogenous approaches in diet-induced obese mice, and analyzed whether changes in the gut microbiota could account for the impact of oral n-3 PUFA on NAFLD. In the model of supplementation, C57Bl/6J mice were fed a high-fat (HF) diet and gavaged daily with either n-6- or n-3-rich oil. In parallel, hemizygous fat-1 (+/−) mice were also fed with the same HF diet and gavaged with the n-6-rich oil. The protocol was conducted over 12 weeks and included physiological tests. Our data show that diet-induced hepatic steatosis and inflammation are abrogated whereas neither insulin resistance nor glucose tolerance are prevented in mice gavaged with fish oil. Conversely, endogenous production of n-3 PUFA in fat-1 mice significantly improved glucose homeostasis but failed to protect against hepatic steatosis. Both routes of increased n-3 PUFA availability reduced plasma cholesterol and improve diet-induced intestinal disturbances, highlighted by the increased abundance of the Allobaculum genus. However, oral n-3 PUFA supplementation was found to more profoundly reshape the gut microbiome, as revealed by major shifts in microbial populations, PiCRUST data, bile acids and short-chain fatty acid production. These results reveal that oral and endogenous n-3 PUFA administration can lead to distinct but also overlapping immunometabolic benefits. However, oral supplementation appears to be required to elicit major shifts in the gut microbiome and prevent hepatic steatosis and inflammation. This project demonstrates a key role of the gut-liver axis in the preventive effect of n-3 PUFA on NAFLD.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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