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

Yue Yang; Bin Huang; Yimeng Qinx; Yimeng Qin; Danwei Wang; Yinuo Jin; Linmin Su; Qingxin Wang; Yi Pan; Yanfeng Zhang; Yumeng Shen; Wenjun Hu; Zhengyu Cao; Liang Jin; Fangfang Zhang

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 (Mir802) expression in adipose tissue is progressively increased with the development of dietary obesity in obese mice and humans. The increasing trend of Mir802 preceded the accumulation of macrophages. Adipose tissue-specific knockout of Mir802 lowered macrophage infiltration and ameliorated systemic insulin resistance. Conversely, the specific overexpression of Mir802 in adipose tissue aggravated adipose inflammation in mice fed a high-fat diet. Mechanistically, Mir802 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 Mir802 endows adipose tissue with the ability to recruit and polarize macrophages, which underscores Mir802 as an innovative and attractive candidate for miRNA-based immune therapy for adipose inflammation.

INSULIN resistance; HIGH-fat diet; METABOLIC disorders; FAT cells; MACROPHAGES; ADIPOSE tissues

eLife, 2024, p1

2050-084X

Academic Journal

10.7554/eLife.99162