title: Muscle-specific downregulation of GR levels inhibits adipogenesis in porcine intramuscular adipocyte tissue.
abstract: Intramuscular adipose is conducive to good pork quality, whereas subcutaneous adipose is considered as waste in pig production. So uncovering the regulation differences between these two adiposes is helpful to tissue-specific control of fat deposition. In this study, we found the sensitivity to glucocorticoids (GCs) was lower in intramuscular adipocytes (IMA) compared with subcutaneous adipocytes (SA). Comparison of glucocorticoid receptor (GR) revealed that IMA had lower GR level which contributed to its reduced GCs sensitivity. Higher methylation levels of GR promotor 1-C and 1-H were detected in IMA compared with SA. GR expression decrease was also found in adipocytes when treated with muscle conditioned medium (MCM) in vitro, which resulted in significant inhibition of adipocytes proliferation and differentiation. Since abundant myostatin (MSTN) was detected in MCM by ELISA assay, we further investigated the effect of this myokine on adipocytes. MSTN treatment suppressed adipocytes GR expression, cell proliferation and differentiation, which mimicked the effects of MCM. The methylation levels of GR promotor 1-C and 1-H were also elevated after MSTN treatment. Our study reveals the role of GR in muscle fiber inhibition on intramuscular adipocytes, and identifies myostatin as a muscle-derived modulator for adipose GR level.
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P.R. China.|Precision Medicine and Healthcare, Tsinghua-Berkeley Shenzhen Institute, Shenzhen, 518055, P.R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Chu
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P.R. China.
authors.forename: Haiyin
authors.initials: H
authors.lastname: Han
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P.R. China.
authors.forename: Kaiqing
authors.initials: K
authors.lastname: Liu
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P.R. China.
authors.forename: Zaohang
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P.R. China.
authors.forename: Lifan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P.R. China. jiechen@njau.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D050156:Adipogenesis; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019175:DNA Methylation / Q000187:drug effects; D015536:Down-Regulation; D005091:Exons / Q000235:genetics; D009132:Muscles / Q000378:metabolism*; D055435:Myostatin / Q000378:metabolism; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000166:cytology; D034421:Sus scrofa
chemical_list: D017077:Culture Media, Conditioned; D055435:Myostatin; D011965:Receptors, Glucocorticoid