title: Glucocorticoid Receptor Mediates the Effect of High-Fat Diet on Mitochondrial Oxidative Phosphorylation in Mouse Liver.
abstract: Obesity is associated with hepatic mitochondrial dysfunction. The relationship between glucocorticoids (GCs) and obesity has also been demonstrated in several researches. Recent research showed that GCs can affect the mitochondrial function. However, the role of glucocorticoid receptor (GR) in obesity-induced mitochondrial dysfunction remains unclear. C57BL/6 male mice fed with a high-fat diet (HFD) for 7 weeks were used as a model. The mice were shown to be overweight, together with lower serum and hepatic corticosterone levels. The hepatic expressions of mitochondrial DNA (mtDNA)-encoded genes were lower in the HFD mice, same as the mtDNA copy number, ATP content, and COX enzyme activity. Both the translocation of GR (NR3C1) into mitochondria and the binding of GR to the mtDNA were lower in the liver of HFD mice. The PGC1α mRNA expression, protein content, and translocation into mitochondria were also found to be reduced, with the lower GR binding to the promoter region of PGC1α in the liver of HFD mice. GR, as a transcription factor, may take an important role in the regulation of mitochondrial oxidative phosphorylation in the HFD mice by interacting with PGC1α and controlling mtDNA expression.
authors.affiliation: 1 Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University , Nanjing, People's Republic of China .
authors.forename: Runsheng
authors.initials: R
authors.lastname: Li
authors.affiliation: 1 Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University , Nanjing, People's Republic of China .
authors.forename: Yimin
authors.initials: Y
authors.lastname: Jia
authors.affiliation: 1 Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University , Nanjing, People's Republic of China .|2 College of Veterinary Medicine, Yangzhou University , Yangzhou, People's Republic of China .
authors.forename: Shifeng
authors.initials: S
authors.lastname: Pan
authors.affiliation: 1 Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University , Nanjing, People's Republic of China .
authors.forename: Xian
authors.initials: X
authors.lastname: Li
authors.affiliation: 1 Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University , Nanjing, People's Republic of China .
authors.forename: Haogang
authors.initials: H
authors.lastname: Song
authors.affiliation: 1 Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University , Nanjing, People's Republic of China .
authors.forename: Ruqian
authors.initials: R
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; C575863:NR3C1 protein, mouse; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D014280:Triglycerides; D002784:Cholesterol