miRNAs in Human Subcutaneous Adipose Tissue: Effects of Weight Loss Induced by Hypocaloric Diet and Exercise

Obesity (Silver Spring). 2017 Mar;25(3):572-580. doi: 10.1002/oby.21765. Epub 2017 Feb 3.

Abstract

Objective: Obesity is central in the development of insulin resistance. However, the underlying mechanisms still need elucidation. Dysregulated microRNAs (miRNAs; post-transcriptional regulators) in adipose tissue may present an important link.

Methods: The miRNA expression in subcutaneous adipose tissue from 19 individuals with severe obesity (10 women and 9 men) before and after a 15-week weight loss intervention was studied using genome-wide microarray analysis. The microarray results were validated with RT-qPCR, and pathway enrichment analysis of in silico predicted targets was performed to elucidate the biological consequences of the miRNA dysregulation. Lastly, the messenger RNA (mRNA) and/or protein expression of multiple predicted targets as well as several proteins involved in lipolysis were investigated.

Results: The intervention led to upregulation of miR-29a-3p and miR-29a-5p and downregulation of miR-20b-5p. The mRNA and protein expression of predicted targets was not significantly affected by the intervention. However, negative correlations between miR-20b-5p and the protein levels of its predicted target, acyl-CoA synthetase long-chain family member 1, were observed. Several other miRNA-target relationships correlated negatively, indicating possible miRNA regulation, including miR-29a-3p and lipoprotein lipase mRNA levels. Proteins involved in lipolysis were not affected by the intervention.

Conclusions: Weight loss influenced several miRNAs, some of which were negatively correlated with predicted targets. These dysregulated miRNAs may affect adipocytokine signaling and forkhead box protein O signaling.

MeSH terms

  • Adult
  • Diet, Reducing*
  • Down-Regulation
  • Exercise*
  • Feeding Behavior
  • Female
  • Gene Expression Regulation
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Obesity / genetics
  • Obesity / metabolism*
  • Obesity / therapy*
  • Subcutaneous Fat / metabolism*
  • Treatment Outcome
  • Weight Loss / physiology*

Substances

  • MicroRNAs