Adipocyte microRNA-802 promotes adipose tissue inflammation and insulin resistance by modulating macrophages in obesity

Abstract

Adipose tissue inflammation is now considered to be a key process underlying metabolic diseases in obese individuals. However, it remains unclear how adipose inflammation is initiated and maintained or the mechanism by which inflammation develops. We found that microRNA-802 (miR-802) expression in adipose tissue is progressively increased with the development of dietary obesity in obese mice and humans. The increasing trend of miR-802 preceded the accumulation of macrophages. Adipose tissue-specific knockout of miR-802 lowered macrophage infiltration and ameliorated systemic insulin resistance. Conversely, the specific overexpression of miR-802 in adipose tissue aggravated adipose inflammation in mice fed a high-fat diet. Mechanistically, miR-802 activates noncanonical and canonical NF-{kappa}B pathways by targeting its negative regulator, TRAF3. Next, NF-{kappa}B orchestrated the expression of chemokine and SREBP1, which translated into strong recruitment and M1-like polarization of macrophages. Our findings indicate that miR-802 endows adipose tissue with the ability to recruit and polarize macrophages, which underscores miR-802 as an innovative and attractive candidate for miRNA-based immune therapy for adipose inflammation.