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

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).

The following data sets were generated

Article and author information

Author details

  1. Yue Yang

    State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Bin Huang

    State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Yimeng Qin

    State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Danwei Wang

    State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Yinuo Jin

    NanJing HanKai Academy, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Linmin Su

    State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Qingxin Wang

    State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Yi Pan

    State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Yanfeng Zhang

    State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  10. yumeng shen

    State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Wenjun Hu

    State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Zhengyu Cao

    School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
    For correspondence
    zycao1999@hotmail.com
    Competing interests
    The authors declare that no competing interests exist.
  13. Liang Jin

    State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
    For correspondence
    ljstemcell@cpu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4995-3553
  14. Fangfang Zhang

    State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
    For correspondence
    1620194592@cpu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1954-4345

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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  1. Yue Yang
  2. Bin Huang
  3. Yimeng Qin
  4. Danwei Wang
  5. Yinuo Jin
  6. Linmin Su
  7. Qingxin Wang
  8. Yi Pan
  9. Yanfeng Zhang
  10. yumeng shen
  11. Wenjun Hu
  12. Zhengyu Cao
  13. Liang Jin
  14. Fangfang Zhang
(2024)
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

Share this article

https://doi.org/10.7554/eLife.99162

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