Adipocyte microRNA-802 promotes adipose tissue inflammation and insulin resistance by modulating macrophages in obesity
- China Pharmaceutical University, China
- NanJing HanKai Academy, China
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 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.
Data availability
Sequencing data have been deposited in the NCBI's Sequence Read Archive (SRA) database (PRJNA1021754).
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RNA-sequ raw dataNCBI SRA, PRJNA1021754.
Article and author information
Author details
Funding
National Natural Science Foundation of China (82100858,82370804)
- Fangfang Zhang
National Natural Science Foundation of China (82373925,82070801)
- Liang Jin
National Natural Science Foundation of China (82073227)
- Yi Pan
Natural Science Foundation of Jiangsu Province (BK20221520)
- Liang Jin
Natural Science Foundation of Jiangsu Province (BK20200569)
- Fangfang Zhang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Care of all animals was within institutional animal-care committee guidelines, and all procedures were approved by the animal ethics committee of China Pharmaceutical University (Permit Number: 2162326) and were in accordance with the international laws and policies (EEC Council Directive 86/609,1987).
Human subjects: All human subjects provided informed consent. All human studies were conducted according to the principles of the Declaration of Helsinki and were approved by the Ethics Committees of the Department Sir Run Run Hospital (Nanjing, China, 2023-SR-046).
Copyright
© 2024, Yang et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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Adipocyte microRNA-802 promotes adipose tissue inflammation and insulin resistance by modulating macrophages in obesity
eLife 13:e99162.
https://doi.org/10.7554/eLife.99162
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