{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T07:13:06Z","timestamp":1786864386116,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sofiproteol","award":["N.A."],"award-info":[{"award-number":["N.A."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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\u2013feeding 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\u2013biochemical mechanistic links.<\/jats:p>","DOI":"10.3390\/nu12123864","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T10:42:47Z","timestamp":1608201767000},"page":"3864","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["An Integrated Analysis of miRNA and Gene Expression Changes in Response to an Obesogenic Diet to Explore the Impact of Transgenerational Supplementation with Omega 3 Fatty Acids"],"prefix":"10.3390","volume":"12","author":[{"given":"Karla Fabiola","family":"Corral-Jara","sequence":"first","affiliation":[{"name":"Unit\u00e9 de Nutrition Humaine (UNH), Universit\u00e9 Clermont Auvergne, Institut National de Recherche pour L\u2019agriculture, L\u2019alimentation et L\u2019environnement (INRAE), Facult\u00e9 de M\u00e9decine, F-63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6360-4440","authenticated-orcid":false,"given":"Laura","family":"Cantini","sequence":"additional","affiliation":[{"name":"Computational Systems Biology Team, Institut de Biologie de l\u2019Ecole Normale Sup\u00e9rieure, CNRS, INSERM, Ecole Normale Sup\u00e9rieure, Universit\u00e9 PSL, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3393-1405","authenticated-orcid":false,"given":"Nathalie","family":"Poupin","sequence":"additional","affiliation":[{"name":"Toxalim (Research Centre in Food Toxicology), Universit\u00e9 de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3394-2083","authenticated-orcid":false,"given":"Tao","family":"Ye","sequence":"additional","affiliation":[{"name":"GenomEast Platform, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), 1 rue Laurent Fries\/BP 10142\/, 67404 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Paul","family":"Rigaudi\u00e8re","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Nutrition Humaine (UNH), Universit\u00e9 Clermont Auvergne, Institut National de Recherche pour L\u2019agriculture, L\u2019alimentation et L\u2019environnement (INRAE), Facult\u00e9 de M\u00e9decine, F-63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah De Saint","family":"Vincent","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Nutrition Humaine (UNH), Universit\u00e9 Clermont Auvergne, Institut National de Recherche pour L\u2019agriculture, L\u2019alimentation et L\u2019environnement (INRAE), Facult\u00e9 de M\u00e9decine, F-63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Pinel","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Nutrition Humaine (UNH), Universit\u00e9 Clermont Auvergne, Institut National de Recherche pour L\u2019agriculture, L\u2019alimentation et L\u2019environnement (INRAE), Facult\u00e9 de M\u00e9decine, F-63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9atrice","family":"Morio","sequence":"additional","affiliation":[{"name":"CarMeN Laboratory, INSERM U1060, INRAE U1397, Universit\u00e9 Lyon 1, 69310 Pierre B\u00e9nite, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0133-0277","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Capel","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Nutrition Humaine (UNH), Universit\u00e9 Clermont Auvergne, Institut National de Recherche pour L\u2019agriculture, L\u2019alimentation et L\u2019environnement (INRAE), Facult\u00e9 de M\u00e9decine, F-63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1373\/clinchem.2007.100156","article-title":"The perfect storm: Obesity, adipocyte dysfunction, and metabolic consequences","volume":"54","author":"Mozaffarian","year":"2008","journal-title":"Clin. 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