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

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