title: Glucocorticoid receptor positively regulates transcription of FNDC5 in the liver.
abstract: Irisin is secreted by skeletal muscle during exercise and influences energy and metabolic homeostasis. This hormone is a cleaved and secreted fragment of fibronectin type III domain-containing 5 (FNDC5). Elucidation of the FNDC5 gene regulation mechanism is necessary to clarify the function of irisin as a potential therapeutic target in human metabolic diseases. Thus, we investigated the genetic and epigenetic mechanisms that regulate expression of the FNDC5 gene. FNDC5 mRNA was strong expressed in major energy-dependent human tissues, including heart, brain, liver, and skeletal muscle. Promoter analysis of the FNDC5 gene revealed that the core promoter region of the FNDC5 gene contained one CpG island that was located just upstream of the transcriptional start site for variants 2 and 3. Treatment with the histone deacetylase inhibitor sodium butyrate and the demethylating agent 5-azacytidine increased mRNA expression of FNDC5 in Huh7 cells. Prediction of transcription factor binding sites suggested that the glucocorticoid receptor was involved in the regulation of FNDC5 expression, and indeed, cortisol treatment increased mRNA expression of FNDC5 in Huh7 cells. Collectively, these findings offer insight into the genetic and epigenetic regulation of FNDC5, providing the initial steps required for understanding the role of irisin in the metabolic homeostasis.
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 plus Project Team, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.|Department of Integrated Biomedical Science, College of Medicine, Inje University, Busan, Korea.
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 plus Project Team, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.
authors.forename: Yu Jeong
authors.initials: YJ
authors.lastname: Jeong
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 plus Project Team, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.|Department of Biomedical Sciences, College of Medicine, Ulsan University, Asan Medical Center, Republic of Korea.
authors.forename: In-Sung
authors.initials: IS
authors.lastname: Song
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 plus Project Team, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Noh
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 plus Project Team, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.
authors.forename: Kyo Won
authors.initials: KW
authors.lastname: Seo
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 plus Project Team, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Kim
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 plus Project Team, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000072283:A549 Cells; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020148:Butyric Acid / Q000494:pharmacology; D002460:Cell Line; D018899:CpG Islands; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D044127:Epigenesis, Genetic; D005353:Fibronectins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D056945:Hep G2 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C577593:FNDC5 protein, human; C571428:FNDC5 protein, mouse; D005353:Fibronectins; D056572:Histone Deacetylase Inhibitors; D011965:Receptors, Glucocorticoid; D020148:Butyric Acid; D006655:Histone Deacetylases; D001374:Azacitidine; D006854:Hydrocortisone