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Loss of miR-146b-3p Inhibits Perivascular Adipocyte Browning with Cold Exposure During Aging

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Abstract

Purpose

Pathological changes of the perivascular adipose tissue (PVAT) are directly associated with increased risk of age-related vascular diseases. MicroRNAs regulate adipocyte biological functions including adipogenic differentiation and white adipocyte browning. The present study aims to determine whether miR-146b-3p is involved in the regulation of perivascular adipocyte browning during aging.

Methods

We utilized a cold-induced animal model to investigate the effect of aging on perivascular adipocyte browning. We also detected the miR-146b-3p expression in the PVAT of young or old mice after cold stimulus. We further investigated the role of miR-146b-3p in regulating perivascular adipocyte browning in vitro and in vivo via administrating miRNA mimics or inhibitors.

Results

Old mice showed decrease of perivascular adipocyte browning and downregulation of miR-146b-3p expression in the PVAT after cold stimulus. Oil red O staining and qPCR indicated that aging perturbed preadipocyte to brown adipocyte differentiation, and expression of miR-146b-3p gradually increased during differentiation. MiR-146b-3p inhibitors blocked brown adipocyte differentiation in young preadipocytes, whereas miR-146b-3p mimics rescued the differentiation of the old preadipocytes. Finally, miR-146b-3p knocks down inhibited perivascular adipocyte browning in young mice after cold stimulus.

Conclusion

Aging inhibits perivascular adipocyte browning, and loss of miR-146b-3p is a potential regulator for this process.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (91539202, 81570221, 81770495, and 91739303), the Shanghai Municipal Commission of Health and Family Planning (2017YQ076 and 201540222), and the Natural Science Foundation of Shanghai, China (16ZR1430900).

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Authors and Affiliations

  1. State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension, Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Xiao-Xi Pan, Cheng-Chao Ruan & Ping-Jin Gao

  2. Department of Geriatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Jiu-Mei Cao, Fan Cai & Fang Wu

Authors
  1. Xiao-Xi Pan
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  2. Jiu-Mei Cao
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  3. Fan Cai
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  4. Cheng-Chao Ruan
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  5. Fang Wu
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  6. Ping-Jin Gao
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Correspondence to Cheng-Chao Ruan or Fang Wu.

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The authors declare that they have no conflict of interest.

Ethical Approval

All animal procedures described in this study were approved in accordance with institutional guidelines established by the Committee of Ethics on Animal Experiments at the Shanghai Jiao Tong University School of Medicine. No human studies were carried out by the authors for this article.

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Pan, XX., Cao, JM., Cai, F. et al. Loss of miR-146b-3p Inhibits Perivascular Adipocyte Browning with Cold Exposure During Aging. Cardiovasc Drugs Ther 32, 511–518 (2018). https://doi.org/10.1007/s10557-018-6814-x

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  • DOI: https://doi.org/10.1007/s10557-018-6814-x

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