MiRNA-181a regulates adipogenesis by targeting tumor necrosis factor-α (TNF-α) in the porcine model

PLoS One. 2013 Oct 1;8(10):e71568. doi: 10.1371/journal.pone.0071568. eCollection 2013.

Abstract

Adipogenesis is tightly regulated by altering gene expression, and TNF-α is a multifunctional cytokine that plays an important role in regulating lipogenesis. MicroRNAs are strong post-transcriptional regulators of cell differentiation. In our previous work, we found high expression of miR-181a in a fat-rich pig breed. Using bioinformatic analysis, miR-181a was identified as a potential regulator of TNF-α. Here, we validated TNF-α as the target of miR-181a by a dual luciferase assay. In response to adipogenesis, a mimic or inhibitor was used to overexpress or reduce miR-181a expression in porcine pre-adipocytes, which were then induced into mature adipocytes. Overexpression of miR-181a accelerated accumulation of lipid droplets, increased the amount of triglycerides, and repressed TNF-α protein expression, while the inhibitor had the opposite effect. At the same time, TNF-alpha rescued the increased lipogenesis by miR181a mimics. Additionally, miR-181a suppression decreased the expression of fatty synthesis associated genes PDE3B (phosphodiesterase 3B), LPL (lipoprotein lipase), PPARγ (proliferator-activated receptor-γ), GLUT1 (glucose transporter), GLUT4, adiponectin and FASN (fatty acid synthase), as well as key lipolytic genes HSL (hormone-sensitive lipase) and ATGL (adipose triglyceride lipase) as revealed by quantitative real-time PCR. Our study provides the first evidence of the role of miR-181a in adipocyte differentiation by regulation of TNF-α, which may became a new therapeutic target for anti-obesity drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Adipogenesis / genetics*
  • Animals
  • Base Sequence
  • Cell Line
  • Gene Expression Regulation / genetics
  • Genes, Reporter / genetics
  • Humans
  • Luciferases / genetics
  • MicroRNAs / genetics*
  • Swine*
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • Tumor Necrosis Factor-alpha
  • Luciferases

Grant support

This work was supported by grants from the Chinese Key Basic Plan (No. 2009CB941600), Chinese 973 Plan (2011CB944202); the Chinese Transgenic breeding Key Project, (2014ZX08009-048B); and the National Natural Science Foundation of China (31072105). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.