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MicroRNA-99a: a potential double-edged sword targeting macrophage inflammation and metabolism

Cellular & Molecular Immunology volume 18, pages 2290–2292 (2021)Cite this article

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In a recent study published in Cellular and Molecular Immunology, Jaiswal et al. demonstrated the importance of microRNA-99a (miR-99a) in adipose tissue inflammation and macrophage phenotype activation [1]. In this study, miR-99a mimics inhibited the M1 macrophage phenotype and adipose tissue inflammation by targeting TNFα, which was accompanied by an improvement in diabetic dyslipidemia and insulin signaling [2]. This study highlights the therapeutic importance of miR-99a in metabolic diseases in which inflammation is a key player.

Targeting inflammation and the adipose tissue microenvironment is an ongoing strategy in understanding and designing therapeutic strategies for lifestyle- or obesity-dependent diabetes [3, 4]. Although reports suggest that local insulin resistance occurs before inflammation and vice versa [5, 6], based on several findings, there is a consensus that insulin resistance can be reversed by limiting inflammation. Some of the anti-inflammatory interventions that have gone to clinical trials include IKKε, TBK1 inhibitors, GPR-120 agonists, CCR-2 antagonists, LTB4R1 inhibitors, TNF inhibitors (etanercept, infliximab) and CRP, TNF, and IL‑6 suppressors (salicylate and aspirin) [4].

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References

  1. Jaiswal A, Reddy SS, Maurya M, Maurya P, Barthwal MK. MicroRNA-99a mimics inhibit M1 macrophage phenotype and adipose tissue inflammation by targeting TNFalpha. Cell Mol Immunol. 2019;16:495–507.

    Article  CAS  Google Scholar 

  2. Gupta P, Barthwal MK. IL-1 beta genesis: the art of regulating the regulator. Cell Mol Immunol. 2018;15:998–1000.

    Article  CAS  Google Scholar 

  3. Appari M, Channon KM, McNeill E. Metabolic regulation of adipose tissue macrophage function in obesity and diabetes. Antioxid Redox Signal. 2018;29:297–312.

    Article  CAS  Google Scholar 

  4. Kusminski CM, Bickel PE, Scherer PE. Targeting adipose tissue in the treatment of obesity-associated diabetes. Nat Rev Drug Discov. 2016;15:639–60.

    Article  CAS  Google Scholar 

  5. Shimobayashi M, Albert V, Woelnerhanssen B, Frei IC, Weissenberger D, Meyer-Gerspach AC, et al. Insulin resistance causes inflammation in adipose tissue. J Clin Investig. 2018;128:1538–50.

    Article  Google Scholar 

  6. Johnson AM, Olefsky JM. The origins and drivers of insulin resistance. Cell. 2013;152:673–84.

    Article  CAS  Google Scholar 

  7. Fujisaka S. The role of adipose tissue M1/M2 macrophages in type 2 diabetes mellitus. Diabetol Int. 2021;12:74–9.

    Article  Google Scholar 

  8. Hui X, Gu P, Zhang J, Nie T, Pan Y, Wu D, et al. Adiponectin enhances cold-induced browning of subcutaneous adipose tissue via promoting M2 macrophage proliferation. Cell Metab. 2015;22:279–90.

    Article  CAS  Google Scholar 

  9. Odegaard JI, Ricardo-Gonzalez RR, Red Eagle A, Vats D, Morel CR, Goforth MH, et al. Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab. 2008;7:496–507.

    Article  CAS  Google Scholar 

  10. Kim A, Saikia P, Nagy LE. miRNAs involved in M1/M2 hyperpolarization are clustered and coordinately expressed in alcoholic hepatitis. Front Immunol. 2019;10:1295.

    Article  CAS  Google Scholar 

  11. Arner P, Kulyte A. MicroRNA regulatory networks in human adipose tissue and obesity. Nat Rev Endocrinol. 2015;11:276–88.

    Article  CAS  Google Scholar 

  12. Heneghan HM, Miller N, McAnena OJ, O’Brien T, Kerin MJ. Differential miRNA expression in omental adipose tissue and in the circulation of obese patients identifies novel metabolic biomarkers. J Clin Endocrinol Metab. 2011;96:E846–850.

    Article  CAS  Google Scholar 

  13. Li Q, Xie J, Wang B, Li R, Bai J, Ding L, et al. Overexpression of microRNA-99a Attenuates Cardiac Hypertrophy. PLoS ONE. 2016;11:e0148480.

    Article  Google Scholar 

  14. Li Q, Xie J, Li R, Shi J, Sun J, Gu R, et al. Overexpression of microRNA-99a attenuates heart remodelling and improves cardiac performance after myocardial infarction. J Cell Mol Med. 2014;18:919–28.

    Article  CAS  Google Scholar 

  15. Tao Z, Zhao H, Wang R, Liu P, Yan F, Zhang C, et al. Neuroprotective effect of microRNA-99a against focal cerebral ischemia-reperfusion injury in mice. J Neurol Sci. 2015;355:113–9.

    Article  CAS  Google Scholar 

  16. Lee, EB, Sung PS, Kim JH, Park DJ, Hur W, Yoon SK. microRNA-99a restricts replication of hepatitis C virus by targeting mTOR and de novo lipogenesis. Viruses. 2020;12:696.

  17. Jiang H, Westerterp M, Wang C, Zhu Y, Ai D. Macrophage mTORC1 disruption reduces inflammation and insulin resistance in obese mice. Diabetologia. 2014;57:2393–404.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Counsil of Scientific and Industrial Research-Central Drug Research Institution, Lucknow, India

    Mohita Maurya & Manoj Kumar Barthwal

  2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India

    Manoj Kumar Barthwal

Authors
  1. Mohita Maurya
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  2. Manoj Kumar Barthwal
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Contributions

MM prepared graphical abstract. MKB wrote and finalized the manuscript and graphical abstract. This manuscript has CSIR-CDRI communication no 10264.

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Correspondence to Manoj Kumar Barthwal.

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The authors declare no competing interests.

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Maurya, M., Barthwal, M.K. MicroRNA-99a: a potential double-edged sword targeting macrophage inflammation and metabolism. Cell Mol Immunol 18, 2290–2292 (2021). https://doi.org/10.1038/s41423-021-00745-1

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