Adipocyte microRNA-802 promotes adipose tissue inflammation and insulin resistance by modulating macrophages in obesity
Yue Yang,
Bin Huang,
Yimeng Qin,
Danwei Wang,
Yinuo Jin,
Linmin Su,
Qingxin Wang,
Yi Pan,
Yanfeng Zhang,
Yumeng Shen,
Wenjun Hu,
Zhengyu Cao,
Liang Jin,
Fangfang Zhang
Affiliations
Yue Yang
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University, Nanjing, China
Bin Huang
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University, Nanjing, China
Yimeng Qin
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University, Nanjing, China
Danwei Wang
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University, Nanjing, China
Yinuo Jin
NanJing HanKai Academy, Nanjing, China
Linmin Su
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University, Nanjing, China
Qingxin Wang
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University, Nanjing, China
Yi Pan
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University, Nanjing, China
Yanfeng Zhang
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University, Nanjing, China
Yumeng Shen
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
Wenjun Hu
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University, Nanjing, China
Zhengyu Cao
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University, Nanjing, China
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University, Nanjing, China
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.
