2UNH - Unité de Nutrition Humaine (Site INRAE Theix : 63122 Saint-Gènes-Champanelle // Site Clermont : UFR de Médecine et de Pharmacie, TSA 50400, 28 Place Henri Dunant, 63001 Clermont-Ferrand - France)
Abstract : Context: Obesity alters adipose tissue's metabolic and endocrine functions and causes a chronic local and systemic low-grade inflammatory state to develop, generating obesity-associated complications. In the last decade, many entities contributing to and regulating this inflammatory state have been identified, among which are microRNAs. Objective: This study aimed to identify microRNA regulated in inflamed adipocytes and adipose tissue, and its effect on adipocyte biology. Design and Results: We screened the expression profile of TNF␣-treated adipocytes (a major pro-inflammatory protein expressed in obese adipose tissue), and identified miR-155 as the most responsive microRNA. The involvement of TNF␣ on the basal miR-155 expression was confirmed in the adipose tissue of Tnfa Ϫ/Ϫ mice where miR-155 was significantly reduced. Also, mice overexpressing p65 or invalidated for p65 in adipose tissue respectively increased and decreased miR-155 expression, in line with the involvement of the nuclear factor B (NF-B) pathway in miR-155 induction. miR-155 expression was higher in obese subjects' adipose tissue than in that of normal-weight subjects, and correlated with TNF␣ expression and body mass index. Gain and loss of function of miR-155 showed its effect on adipocyte function, probably via its ability to target PPAR␥ mRNA 3ЈUTR. Interestingly, miR-155 over-expression also resulted in an increased inflammatory state in adipocytes. Conclusion: Altogether, these data are evidence of a proinflammatory loop mediated by NF-B and miR-155 that could participate in the amplification of inflammatory status in adipocytes. (J Clin Endocrinol Metab 101: 1615-1626, 2016)
https://www.hal.inserm.fr/inserm-01478345
Contributor : Patrick Borel <>
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