title: Adipocyte miR-200b/a/429 ablation in mice leads to high-fat-diet-induced obesity.
abstract: Growing evidence demonstrates the important role of microRNAs (miRs) in regulating adipogenesis, obesity and insulin resistance. The miR-200b/a/429 cluster has been functionally characterized in mammalian reproduction; however, the potential role of the miR-200 family in adipocytes is poorly understood. The aim of our study was to investigate the physiological function of miR-200b/a/429 in the regulation of whole-body metabolism in terms of the activities and targets of this cluster in adipocytes. We generated adipocyte-specific miR-200b/a/429 knockout (ASKO) mice using a Cre-loxP system in which Cre expression was driven by the aP2 promoter. The ASKO and wild type (WT) littermate were fed a chow diet (CD) or high-fat-diet (HFD), and changes in body composition, metabolic parameters, energy homeostasis, glucose tolerance and insulin sensitivity were analyzed. The miR-200b/a/429 putative target genes were predicted and validated via luciferase reporter assays. We found that the HFD-fed ASKO mice gradually gained more body weight than the WT mice due to the increased adiposity. Decreased glucose tolerance and insulin sensitivity were also observed in the HFD-fed ASKO mice. Notably, the down-regulation of lipolysis-related genes and the decreased response to CL-316,243 stimulation in the HFD-fed ASKO mice suggested that these animals exhibited impaired lipolysis. In addition, the HFD-fed ASKO mice displayed impaired energy expenditure, indicating that the miR-200b/a/429 cluster is essential for developing adaptive responses to stressors such as HFD. For the first time, our studies demonstrated the essential role of miR-200b/a/429 in adipocytes in the regulation of HFD-induced whole-body metabolic changes.
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.|College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.|Key Laboratory of Animal Embryo & Molecular Breeding of Hubei Province, Institute of Veterinary and Animal Science, Hubei Academy of Agricultural Science, Wuhan, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Yulian
authors.initials: Y
authors.lastname: Mu
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Shulin
authors.initials: S
authors.lastname: Yang
authors.affiliation: College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China.
authors.forename: Desheng
authors.initials: D
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D004734:Energy Metabolism / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D007333:Insulin Resistance / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D005810:Multigene Family; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C582202:MIRN429 microRNA, mouse; D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse
keywords: Pathology Section; adipose tissue; high-fat-diet; insulin resistance; knockout; miR-200b/a/429