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Obesity-associated Inflammation Induces microRNA-155 Expression in Adipocytes and Adipose Tissue: Outcome on Adipocyte Function

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)
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Esma Karkeni, Julien Astier, Franck Tourniaire, Mouna El Abed, Béatrice Romier, et al.. Obesity-associated Inflammation Induces microRNA-155 Expression in Adipocytes and Adipose Tissue: Outcome on Adipocyte Function. Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2016, 101 (4), pp.1615 - 1626. ⟨10.1210/jc.2015-3410⟩. ⟨inserm-01478345⟩

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