Adipocyte promotes 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 that () expression in adipose tissue is progressively increased with the development of dietary obesity in obese mice and humans. The increasing trend of preceded the accumulation of macrophages. Adipose tissue-specific knockout of lowered macrophage infiltration and ameliorated systemic insulin resistance. Conversely, the specific overexpression of in adipose tissue aggravated adipose inflammation in mice fed a high-fat diet. Mechanistically, 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 endows adipose tissue with the ability to recruit and polarize macrophages, which underscores as an innovative and attractive candidate for miRNA-based immune therapy for adipose inflammation.