Glucocorticoid receptor positively regulates transcription of FNDC5 in the liver

• Published in: Scientific reports 2017-02, Vol.7 (1), p.43296-43296, Article 43296
• Main Authors: Kim, Hyoung Kyu, Jeong, Yu Jeong, Song, In-Sung, Noh, Yeon Hee, Seo, Kyo Won, Kim, Min, Han, Jin
• Format: Article
• Language: English
• Subjects: 13/95; 38/77; 631/208/199; 631/80/86; A549 Cells; Animals; Azacitidine - pharmacology; Azacytidine; Brain - cytology; Brain - drug effects; Brain - metabolism; Butyric Acid - pharmacology; Cell Line; CpG Islands; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Epigenesis, Genetic; Epigenetics; Fibronectin; Fibronectins - agonists; Fibronectins - genetics; Fibronectins - metabolism; Gene regulation; Glucocorticoids; HeLa Cells; Hep G2 Cells; Histone deacetylase; Histone Deacetylase Inhibitors - pharmacology; Histone Deacetylases - genetics; Histone Deacetylases - metabolism; Homeostasis; Humanities and Social Sciences; Humans; Hydrocortisone - pharmacology; Liver; Liver - cytology; Liver - drug effects; Liver - metabolism; Metabolic disorders; Metabolism; Mice; multidisciplinary; Muscle, Skeletal - cytology; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Musculoskeletal system; Myocardium - cytology; Myocardium - metabolism; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Promoter Regions, Genetic; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Science; Skeletal muscle; Sodium butyrate; Transcription, Genetic
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep43296

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.