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J Clin Endocrinol Metab. 2016 Apr;101(4):1615-26. doi: 10.1210/jc.2015-3410. Epub 2016 Feb 1.

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

Author information

1
Institut National de Recherche Agronomique (INRA) (E.K., J.A., F.T., M.E.A., B.R., E.G., P.B., J.-F.L.), UMR 1260, F-13385, Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) 1062 (E.K., J.A., F.T., M.E.A., B.R., E.G., P.B., J.F.L.), Nutrition, Obésité et Risque Thrombotique F-13385, Marseille, France; Faculté de Médecine (E.K., J.A., F.T., M.E.A., B.R., E.G., P.B., J.-F.L.), Aix-Marseille Université, F-13385, Marseille, France; Pennington Biomedical Research Center (L.W., J.Y.), Louisiana State University System, Baton Rouge, LA 70808; Laboratory of Transplant Immunology, Regeneration Medicine Research Center, Sichuan University, Sichuan Province, 610041 China; and UMR INRA 1019 Unité de Nutrition Humaine (J.S., S.W.), Centre de Recherches INRA de Clermont-Ferrand/Theix, 63122 St-Genès-Champanelle, 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 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.

PMID:
26829440
PMCID:
PMC4880153
DOI:
10.1210/jc.2015-3410
[Indexed for MEDLINE]
Free PMC Article

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