title: MicroRNA-375 promotes 3T3-L1 adipocyte differentiation through modulation of extracellular signal-regulated kinase signalling.
abstract: 1. Adipocyte hypertrophy and hyperplasia are important processes in the development of obesity. To understand obesity and its associated diseases, it is important to elucidate the molecular mechanisms governing adipogenesis. MicroRNA-375 has been shown to inhibit differentiation of neurites, and participate in the regulation of insulin secretion and blood homeostasis. However, it is unknown whether miR-375 plays a role in adipocyte differentiation. 2. To investigate the role of miR-375 in adipocyte differentiation, we compared the miR-375 expression level between 3T3-L1 pre-adipocytes and adipocytes using miRNA microarray and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis. Furthermore, we evaluated the effects of overexpression or inhibition of miR-375 on 3T3-L1 adipocyte differentiation. 3. In the present study, we found that miR-375 expression was increased after induction of adipogenic differentiation. Overexpression of miR-375 enhanced 3T3-L1 adipocyte differentiation, as evidenced by its ability to increase mRNA levels of both CCAAT/enhancer binding protein-α (C/EBPα) and peroxisome proliferator-activated receptor-γ (PPARγ2), and induction of adipocyte fatty acid-binding protein (aP2) and triglyceride (TG) accumulation. Furthermore, we found overexpression of miR-375 suppressed phosphorylation levels of extracellular signal-regulated kinases 1/2 (ERK1/2). In contrast, anti-miR-375 increased ERK1/2 phosphorylation levels and inhibited mRNA expression of C/EBPα, PPARγ2 and aP2 in 3T3-L1 adipocyte, accompanied by decreased adipocyte differentiation. 4. Taken together, these data suggest that miR-375 promotes 3T3-L1 adipocyte differentiation, possibly through modulating the ERK-PPARγ2-aP2 pathway.
authors.affiliation: Department of Physiology, School of Medicine, Health Key Laboratory for Pharmacoproteomics of Hunan Province/Institute of Pharmacy and Pharmacology, University of South China, Hengyang, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Ling
authors.forename: Ge-Bo
authors.initials: GB
authors.lastname: Wen
authors.forename: Shui-Dong
authors.initials: SD
authors.lastname: Feng
authors.forename: Qin-Hui
authors.initials: QH
authors.lastname: Tuo
authors.forename: He-Sheng
authors.initials: HS
authors.lastname: Ou
authors.forename: Chao Hua
authors.initials: CH
authors.lastname: Yao
authors.forename: Bing-Yang
authors.initials: BY
authors.lastname: Zhu
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Gao
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Duan-Fang
authors.initials: DF
authors.lastname: Liao
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D035683:MicroRNAs; C540349:Mirn375 microRNA, mouse; D047495:PPAR gamma; D012333:RNA, Messenger; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases