Overexpression of microRNA-9 inhibits 3T3-L1 cell adipogenesis by targeting PNPLA3 via activation of AMPK

Gene. 2020 Mar 10:730:144260. doi: 10.1016/j.gene.2019.144260. Epub 2019 Nov 21.

Abstract

Adipocyte differentiation, which plays an important role in the development of obesity, involves complex molecular networks in which microRNAs (miRNAs) are essential. Here, we show that miR-9 expression was upregulated during adipogenesis in 3T3-L1 cells. miR-9 overexpression reduced the accumulation of lipid droplets and the content of triglycerides by downregulating patatin-like phospholipase domain-containing protein 3 (PNPLA3). PNPLA3 knockdown or miR-9 overexpression downregulated the protein expression of peroxisome proliferator-activated receptor γ, oxidative tissue-enrichedPAT, and LC3, and promoted the phosphorylation of AMP-activated protein kinase (AMPK), which was inhibited by treatment with the AMPK inhibitor compound C. These results indicate that miR-9 inhibits adipocyte differentiation by targeting PNPLA3 through the AMPK pathway.

Keywords: AMPK; Adipogenesis; Autophagy; PNPLA3; miR-9.

MeSH terms

  • 3T3-L1 Cells
  • AMP-Activated Protein Kinases / genetics
  • Adipocytes / metabolism
  • Adipogenesis / genetics*
  • Animals
  • Autophagy / genetics
  • Cell Differentiation / genetics
  • Gene Expression Regulation / genetics
  • Intracellular Signaling Peptides and Proteins / genetics
  • Lipid Droplets / metabolism
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • PPAR gamma / genetics
  • Phospholipases A2, Calcium-Independent / genetics
  • Phospholipases A2, Calcium-Independent / metabolism*
  • Phosphorylation
  • Signal Transduction

Substances

  • Intracellular Signaling Peptides and Proteins
  • MIRN9 microRNA, mouse
  • MicroRNAs
  • OXPAT protein, mouse
  • PPAR gamma
  • AMP-Activated Protein Kinases
  • PNPLA3 protein, mouse
  • Phospholipases A2, Calcium-Independent