miR-148a is Associated with Obesity and Modulates Adipocyte Differentiation of Mesenchymal Stem Cells through Wnt Signaling

• Published in: Scientific reports 2015-05, Vol.5 (1), p.9930-9930, Article 9930
• Main Authors: Shi, Chunmei, Zhang, Min, Tong, Meiling, Yang, Lei, Pang, Lingxia, Chen, Ling, Xu, Guangfeng, Chi, Xia, Hong, Qin, Ni, Yuhui, Ji, Chenbo, Guo, Xirong
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; 692/163/2743/393; 692/700; 96; 96/1; 96/100; 96/109; Adipocytes; Adipocytes - cytology; Adipocytes - metabolism; Adipogenesis; Adipose tissue; Animals; Base Sequence; Cell Differentiation; CREB-Binding Protein - chemistry; CREB-Binding Protein - metabolism; Diet, High-Fat; Ectopic expression; Humanities and Social Sciences; Humans; Immunology; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mesenchyme; Mice; Mice, Inbred C57BL; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; multidisciplinary; Obesity; Obesity - metabolism; Obesity - pathology; Oligonucleotides, Antisense - metabolism; Promoter Regions, Genetic; Protein Binding; Real-Time Polymerase Chain Reaction; Rodents; Science; Sequence Alignment; Stem cells; Wnt Signaling Pathway; Wnt1 Protein - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep09930

Obesity results from numerous, interacting genetic, behavioral and physiological factors. Adipogenesis is partially regulated by several adipocyte-selective microRNAs (miRNAs) and transcription factors that regulate proliferation and differentiation of human adipose-derived mesenchymal stem cells (hMSCs-Ad). In this study, we examined the roles of adipocyte-selective miRNAs in the differentiation of hMSCs-Ad to adipocytes. Results showed that the levels of miR-148a, miR-26b, miR-30, and miR-199a increased in differentiating hMSCs-Ad. Among these miRNAs, miR-148a exhibited significant effects on increasing PPRE luciferase activity (it represents PPAR-dependent transcription, a major factor in adipogenesis) than others. Furthermore, miR-148a expression levels increased in adipose tissues from obese people and mice fed high-fat diet. miR-148a acted by suppressing its target gene, Wnt1, an endogenous inhibitor of adipogenesis. Ectopic expression of miR-148a accelerated differentiation and partially rescued Wnt1-mediated inhibition of adipogenesis. Knockdown of miR-148a also inhibited adipogenesis. Analysis of the upstream region of miR-148a locus identified a 3 kb region containing a functional cAMP-response element-binding protein (CREB) required for miR-148a expression in hMSCs-Ad. The results suggest that miR-148a is a biomarker of obesity in human subjects and mouse model, which represents a CREB-modulated miRNA that acts to repress Wnt1, thereby promoting adipocyte differentiation.