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

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 TNFα-treated adipocytes (a major pro-inflammatory protein expressed in obese adipose tissue), and identified miR-155 as the most responsive microRNA. The involvement of TNFα on the basal miR-155 expression was confirmed in the adipose tissue of Tnfa−/− 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 κB (NF-κB) 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 TNFα 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 PPARγ mRNA 3′UTR. Interestingly, miR-155 overexpression also resulted in an increased inflammatory state in adipocytes. Conclusion: Altogether, these data are evidence of a proinflammatory loop mediated by NF-κB and miR-155 that could participate in the amplification of inflammatory status in adipocytes. miR-155 expression is induced in adipocytes and adipose tissue submitted to inflammatory conditions in obesity context in murine and human models and participate to a pro-inflammatory loop by targeting PPARg.