MicroRNA-27a, downregulated in human obesity, exerts an antiapoptotic function in adipocytes

Endocr J. 2023 Jun 28;70(6):581-589. doi: 10.1507/endocrj.EJ22-0288. Epub 2023 Apr 5.

Abstract

Adipocyte apoptosis is a key initial event that contributes to macrophage infiltration into adipose tissue (AT) and thus triggers AT inflammation in obesity. MicroRNA-27a (miR-27a) was shown to mediate the pathological processes of many metabolic disorders; however, whether miR-27a is involved in adipocyte apoptosis of obese AT remains unknown. The present study aimed to investigate the alteration of miR-27a in obese individuals and its antiapoptotic function in adipocytes. In vivo, serum samples and omental adipose tissue from humans as well as epididymal fat pads from mice were collected to detect miR-27a expression. In vitro, 3T3-L1 preadipocytes and mature adipocytes were treated with TNF-α to induce apoptosis and transfected with a mimic for overexpressing miR-27a-3p. The results showed that miR-27a was markedly decreased in the serum and AT of obese human patients and in the AT of high-fat diet-fed mice. Regression analyses revealed that the serum level of miR-27a was correlated with metabolic parameters in human obesity. Notably, TNF-α induced cell apoptosis in both preadipocytes and mature adipocytes, as evidenced by the upregulation of cleaved caspase 3 and cleaved caspase 8 and the ratio of Bax to Bcl-2, while these effects were partly diminished by miR-27a overexpression. In addition, TUNEL and Hoechst 33258 staining verified that miR-27a overexpression markedly inhibited the apoptosis of adipocytes under TNF-α stimulation. Thus, miR-27a was downregulated in the AT of obese subjects with proapoptotic status, and overexpression of miR-27a exerted an antiapoptotic effect on preadipocytes, providing a novel potential target for preventing AT dysfunction.

Keywords: Adipocytes; Adipose tissue; Apoptosis; Obesity; miR-27a.

MeSH terms

  • Adipocytes / metabolism
  • Animals
  • Humans
  • Mice
  • MicroRNAs* / genetics
  • Obesity
  • Tumor Necrosis Factor-alpha* / metabolism
  • Tumor Necrosis Factor-alpha* / pharmacology

Substances

  • MIRN27 microRNA, rat
  • Tumor Necrosis Factor-alpha
  • MicroRNAs