title: miR-148a is Associated with Obesity and Modulates Adipocyte Differentiation of Mesenchymal Stem Cells through Wnt Signaling.
abstract: 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.
authors.affiliation: 1] Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China [2] Institute of Pediatrics, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Tong
authors.affiliation: 1] Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China [2] Institute of Pediatrics, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: 1] Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China [2] Institute of Pediatrics, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Lingxia
authors.initials: L
authors.lastname: Pang
authors.affiliation: 1] Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China [2] Institute of Pediatrics, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China.
authors.forename: Guangfeng
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Chi
authors.affiliation: Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Hong
authors.affiliation: Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Ni
authors.affiliation: 1] Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China [2] Institute of Pediatrics, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chenbo
authors.initials: C
authors.lastname: Ji
authors.affiliation: 1] Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China [2] Institute of Pediatrics, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xirong
authors.initials: X
authors.lastname: Guo
mesh_terms: D020413:3' Untranslated Regions; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D001483:Base Sequence; D050882:CREB-Binding Protein / Q000737:chemistry / Q000378:metabolism; D002454:Cell Differentiation; D059305:Diet, High-Fat; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D060888:Real-Time Polymerase Chain Reaction; D016415:Sequence Alignment; D060449:Wnt Signaling Pathway; D051155:Wnt1 Protein / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; C495247:WNT1 protein, human; D051155:Wnt1 Protein; D050882:CREB-Binding Protein; C494363:CREBBP protein, human