Adipocyte <i>microRNA-802</i> 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 <i>microRNA-802</i> (<i>Mir802</i>) expression in adipose tissue is progressively increased with the development of dietary obesity in obese mice and humans. The increasing trend of <i>Mir802</i> preceded the accumulation of macrophages. Adipose tissue-specific knockout of <i>Mir802</i> lowered macrophage infiltration and ameliorated systemic insulin resistance. Conversely, the specific overexpression of <i>Mir802</i> in adipose tissue aggravated adipose inflammation in mice fed a high-fat diet. Mechanistically, <i>Mir802</i> activates noncanonical and canonical NF-κB pathways by targeting its negative regulator, TRAF3. Next, NF-κB orchestrated the expression of chemokines and SREBP1, leading to strong recruitment and M1-like polarization of macrophages. Our findings indicate that <i>Mir802</i> endows adipose tissue with the ability to recruit and polarize macrophages, which underscores <i>Mir802</i> as an innovative and attractive candidate for miRNA-based immune therapy for adipose inflammation.