Chronic glucocorticoid exposure-induced epididymal adiposity is associated with mitochondrial dysfunction in white adipose tissue of male C57BL/6J mice

• Published in: PloS one Vol. 9; no. 11; p. e112628
• Main Authors: Yu, Jie, Yu, Bing, He, Jun, Zheng, Ping, Mao, Xiangbing, Han, Guoquan, Chen, Daiwen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.11.2014; Public Library of Science (PLoS)
• Subjects: Adipocytes; Adipose tissue; Adipose Tissue, White - drug effects; Adipose Tissue, White - metabolism; Adiposity - drug effects; Adiposity - physiology; Adrenocorticotropic hormone; Animal diseases; Animals; Bioengineering; Biology and Life Sciences; Biosynthesis; Body fat; Body weight; Body Weight - drug effects; Corticosterone; Corticosterone - blood; Corticosterone - pharmacology; Cushing syndrome; Cushing's syndrome; Dehydrogenases; Drinking water; Eating - drug effects; Education; Energy balance; Enzyme-linked immunosorbent assay; Enzymes; Epididymis - drug effects; Epididymis - metabolism; Ethanol; Exposure; Fatty acids; Fatty Acids, Nonesterified - blood; Fibroblast growth factor; Fibroblast growth factors; Fibroblast Growth Factors - blood; Food intake; Fuel consumption; Gene expression; Glucocorticoids; Glucocorticoids - pharmacology; Homeostasis; Hormones; House mouse; Insulin; Insulin - blood; Laboratories; Leptin; Leptin - blood; Male; Metabolic syndrome; Mice; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial DNA; Nervous system diseases; Nutrition; Obesity; Oxidation; Oxygen; Pituitary; Plasma; Plasma levels; Polymerase chain reaction; Reactive oxygen species; Reactive Oxygen Species - metabolism; Rodents; Steroids (Organic compounds); Triglycerides; Triglycerides - blood; Water intake; Water intakes; United States > US; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0112628

Prolonged and excessive glucocorticoids (GC) exposure resulted from Cushing's syndrome or GC therapy develops central obesity. Moreover, mitochondria are crucial in adipose energy homeostasis. Thus, we tested the hypothesis that mitochondrial dysfunction may contribute to chronic GC exposure-induced epididymal adiposity in the present study. A total of thirty-six 5-week-old male C57BL/6J mice (∼20 g) were administrated with 100 µg/ml corticosterone (CORT) or vehicle through drinking water for 4 weeks. Chronic CORT exposure mildly decreased body weight without altering food and water intake in mice. The epididymal fat accumulation was increased, but adipocyte size was decreased by CORT. CORT also increased plasma CORT, insulin, leptin, and fibroblast growth factor 21 concentrations as measured by RIA or ELISA. Interestingly, CORT increased plasma levels of triacylglycerols and nonesterified fatty acids, and up-regulated the expression of both lipolytic and lipogenic genes as determined by real-time RT-PCR. Furthermore, CORT impaired mitochondrial biogenesis and oxidative function in epididymal WAT. The reactive oxygen species production was increased and the activities of anti-oxidative enzymes were reduced by CORT treatment as well. Taken together, these findings reveal that chronic CORT administration-induced epididymal adiposity is, at least in part, associated with mitochondrial dysfunction in mouse epididymal white adipose tissue.