| Autor: |
Corral-Jara KF; Unité de Nutrition Humaine (UNH), Université Clermont Auvergne, Institut National de Recherche pour L'agriculture, L'alimentation et L'environnement (INRAE), Faculté de Médecine, F-63000 Clermont-Ferrand, France., Cantini L; Computational Systems Biology Team, Institut de Biologie de l'Ecole Normale Supérieure, CNRS, INSERM, Ecole Normale Supérieure, Université PSL, 75005 Paris, France., Poupin N; Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France., Ye T; GenomEast Platform, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 1 rue Laurent Fries/BP 10142/, 67404 Illkirch, France., Rigaudière JP; Unité de Nutrition Humaine (UNH), Université Clermont Auvergne, Institut National de Recherche pour L'agriculture, L'alimentation et L'environnement (INRAE), Faculté de Médecine, F-63000 Clermont-Ferrand, France., De Saint Vincent S; Unité de Nutrition Humaine (UNH), Université Clermont Auvergne, Institut National de Recherche pour L'agriculture, L'alimentation et L'environnement (INRAE), Faculté de Médecine, F-63000 Clermont-Ferrand, France., Pinel A; Unité de Nutrition Humaine (UNH), Université Clermont Auvergne, Institut National de Recherche pour L'agriculture, L'alimentation et L'environnement (INRAE), Faculté de Médecine, F-63000 Clermont-Ferrand, France., Morio B; CarMeN Laboratory, INSERM U1060, INRAE U1397, Université Lyon 1, 69310 Pierre Bénite, France., Capel F; Unité de Nutrition Humaine (UNH), Université Clermont Auvergne, Institut National de Recherche pour L'agriculture, L'alimentation et L'environnement (INRAE), Faculté de Médecine, F-63000 Clermont-Ferrand, France. |
| Abstrakt: |
Insulin resistance decreases the ability of insulin to inhibit hepatic gluconeogenesis, a key step in the development of metabolic syndrome. Metabolic alterations, fat accumulation, and fibrosis in the liver are closely related and contribute to the progression of comorbidities, such as hypertension, type 2 diabetes, or cancer. Omega 3 ( n -3) polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), were identified as potent positive regulators of insulin sensitivity in vitro and in animal models. In the current study, we explored the effects of a transgenerational supplementation with EPA in mice exposed to an obesogenic diet on the regulation of microRNAs (miRNAs) and gene expression in the liver using high-throughput techniques. We implemented a comprehensive molecular systems biology approach, combining statistical tools, such as MicroRNA Master Regulator Analysis pipeline and Boolean modeling to integrate these biochemical processes. We demonstrated that EPA mediated molecular adaptations, leading to the inhibition of miR-34a-5p, a negative regulator of Irs2 as a master regulatory event leading to the inhibition of gluconeogenesis by insulin during the fasting-feeding transition. Omics data integration provided greater biological insight and a better understanding of the relationships between biological variables. Such an approach may be useful for deriving innovative data-driven hypotheses and for the discovery of molecular-biochemical mechanistic links. |
