期刊
OBESITY
卷 25, 期 3, 页码 572-580出版社
WILEY
DOI: 10.1002/oby.21765
关键词
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资金
- Danish Medical Research Council [22-02-0527]
- Novo Nordisk Foundation [NNF14CC0001]
- NORDEA Foundation
- Torben og Alice Frimodts Fond
- Novo Nordisk Foundation Center for Protein Research [PI Lars Juhl Jensen] Funding Source: researchfish
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 genomewide 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 miR20b-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.
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