title: Glucocorticoids transcriptionally regulate miR-27b expression promoting body fat accumulation via suppressing the browning of white adipose tissue.
abstract: Long-term glucocorticoid (GC) treatment induces central fat accumulation and metabolic dysfunction. We demonstrate that microRNA-27b (miR-27b) plays a central role in the pathogenesis of GC-induced central fat accumulation. Overexpression of miR-27b had the same effects as dexamethasone (DEX) treatment on the inhibition of brown adipose differentiation and the energy expenditure of primary adipocytes. Conversely, antagonizing miR-27b function prevented DEX suppression of the expression of brown adipose tissue-specific genes. GCs transcriptionally regulate miR-27b expression through a GC receptor-mediated direct DNA-binding mechanism, and miR-27b suppresses browning of white adipose tissue (WAT) by targeting the three prime untranslated region of Prdm16. In vivo, antagonizing miR-27b function in DEX-treated mice resulted in the efficient induction of brown adipocytes within WAT and improved GC-induced central fat accumulation. Collectively, these results indicate that miR-27b functions as a central target of GC and as an upstream regulator of Prdm16 to control browning of WAT and, consequently, may represent a potential target in preventing obesity.
authors.affiliation: Department of Geratology, The First Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Xiaocen
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Geratology, The First Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Geratology, The First Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Bi
authors.affiliation: Department of Geratology, The First Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Hanmei
authors.initials: H
authors.lastname: Qi
authors.affiliation: Department of Geratology, The First Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Di
authors.affiliation: Department of Geratology, The First Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Geratology, The First Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Geratology, The First Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Juanmin
authors.initials: J
authors.lastname: Zha
authors.affiliation: Department of Geratology, The First Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Lv
authors.affiliation: Department of General Surgery, The First Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Metabolic Syndrome Research Center of Central South University, Institute of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Metabolic Syndrome Research Center of Central South University, Institute of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Hu
authors.affiliation: Metabolic Syndrome Research Center of Central South University, Institute of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Bone Research Program, ANZAC Research Institute, University of Sydney, Sydney, Australia.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Geratology, The First Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China dinggx@njmu.edu.cn lioujane@njmu.edu.cn.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Geratology, The First Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China dinggx@njmu.edu.cn lioujane@njmu.edu.cn.
authors.forename: Guoxian
authors.initials: G
authors.lastname: Ding
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000502:physiology*; D052436:Adipose Tissue, White / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D035683:MicroRNAs; C540674:Mirn27 microRNA, mouse; C521133:Prdm16 protein, mouse; D014157:Transcription Factors; D003907:Dexamethasone