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

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Malene M. Kristensen, Peter K. Davidsen, Andreas Vigelso, Christina N. Hansen, Lars J. Jensen, Niels Jessen, Jens M. Bruun, Flemming Dela, Jorn W. Helge

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.
OriginalsprogEngelsk
TidsskriftObesity
Vol/bind25
Udgave nummer3
Sider (fra-til)572-580
Antal sider9
ISSN1930-7381
DOI
StatusUdgivet - mar. 2017

Bibliografisk note

CURIS 2017 NEXS 371

ID: 183825335