Critical role of miR-125b in lipogenesis by targeting stearoyl-CoA desaturase-1 (SCD-1)

Alteration of gene expression tightly regulates lipogenesis. Stearoyl-CoA desaturase-1 (SCD-1), a key enzyme in lipogenesis, catalyzes the conversion of SFA to MUFA, and inhibition of its activity impairs lipid synthesis. As posttranscriptional regulators, microRNAs are involved in many pathways of...

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Bibliographic Details
Published in:Journal of animal science 2016-01, Vol.94 (1), p.65-76
Main Authors: Cheng, X, Xi, Q-Y, Wei, S, Wu, D, Ye, R-S, Chen, T, Qi, Q-E, Jiang, Q-Y, Wang, S-B, Wang, L-N, Zhu, X-T, Zhang, Y-L
Format: Article
Language:English
Subjects:
Adipocytes - metabolism
Adipogenesis
Animals
Cell Differentiation
Cells, Cultured
Cricetinae
Gene Deletion
Gene Expression Regulation, Enzymologic
Lipid Metabolism - physiology
Lipogenesis - physiology
Liver - metabolism
Male
Mice
MicroRNAs - genetics
MicroRNAs - metabolism
RNA, Small Interfering - metabolism
Stearoyl-CoA Desaturase - genetics
Stearoyl-CoA Desaturase - metabolism
Swine
Triglycerides - metabolism
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Summary:Alteration of gene expression tightly regulates lipogenesis. Stearoyl-CoA desaturase-1 (SCD-1), a key enzyme in lipogenesis, catalyzes the conversion of SFA to MUFA, and inhibition of its activity impairs lipid synthesis. As posttranscriptional regulators, microRNAs are involved in many pathways of lipid metabolism; however, their effect on SCD-1 has not been reported. In this study, miR-125b was identified as a potential regulator of SCD-1 using bioinformatics analysis. Here, we validated SCD-1 as the target of miR-125b using a dual luciferase assay. During adipogenesis, a synthetic mimic or inhibitor was used to overexpress or reduce the expression of miR-125b in porcine adipocytes. Overexpression of miR-125b reduced the accumulation of lipid droplets and triglycerides concentration and repressed SCD-1 protein expression and MUFA composition. The inhibitor had the reverse effect. Small interfering RNA against tested in adipocytes further proved the direct correlation between miR-125b and SCD-1. Moreover, in vivo experiments in mice showed that injection of miR-125b expression vector decreased the hepatic triglycerides concentration relative to saline. This study indicated that miR-125b regulates lipogenesis by targeting SCD-1; therefore, miR-125b might be applied in therapy of lipid metabolism disorders.
ISSN:1525-3163
DOI:10.2527/jas.2015-9456