title: Voluntary exercise protects against ulcerative colitis by up-regulating glucocorticoid-mediated PPAR-γ activity in the colon in mice.
abstract: OBJECTIVE
  Voluntary exercise has been shown to protect against the development of ulcerative colitis, but the mechanism is not fully understood. We hypothesized that prior voluntary exercise would attenuate colonic inflammation and ameliorate clinical symptoms in dextran sulphate sodium (DSS)-induced ulcerative colitis by increasing glucocorticoid production and up-regulating PPAR-γ activity in the colon.
  
  
  METHODS
  Male C57Bl/6J mice were assigned to sedentary, exercise, exercise with PPAR-γ antagonist GW9662 or glucocorticoid synthesis inhibitor metyrapone. Following the completion of the 30 days' exercise training programme, they were treated with or without 2% DSS in drinking water for 5 days, followed by 5 days of regular water.
  
  
  RESULTS
  Compared with sedentary mice, exercise mice exhibited improved clinical symptoms (weight loss and diarrhoea) and less inflammation (expression of pro-inflammatory cytokines and histological injury) in response to DSS, whereas these beneficial effects were abolished by both GW9662 and metyrapone treatment. Molecular studies revealed that exercise significantly increased the expression of PPAR-γ, augmented the expression of steroidogenic enzymes (CYP11A1 and CYP11B1) and elevated corticosterone levels in the colon. GW9662 treatment reversed the expression of PPAR-γ without altering the expression of steroidogenic enzymes and corticosterone secretion in the colon, while metyrapone treatment blocked glucocorticoid secretion and abrogated the increase in PPAR-γ expression in the colon.
  
  
  CONCLUSIONS
  These findings suggest that prior voluntary exercise suppresses the expression of pro-inflammatory cytokines in the colon in response to inflammatory challenge by up-regulating glucocorticoid-mediated PPAR-γ activity, contributing to protection against the development of ulcerative colitis.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: W-X
authors.initials: WX
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: F
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: J-W
authors.initials: JW
authors.lastname: Xing
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: L-X
authors.initials: LX
authors.lastname: Sang
authors.affiliation: Department of Anatomy, Seirei Christopher College, Hamamatsu, Japan.
authors.forename: S-Z
authors.initials: SZ
authors.lastname: Gu
authors.affiliation: Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, Guangdong, China.
authors.forename: H-L
authors.initials: HL
authors.lastname: Wang
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000628:therapy; D003345:Corticosterone / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D015533:Transcriptional Activation / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D047495:PPAR gamma; D003345:Corticosterone
keywords: PPAR-γ activity; glucocorticoid synthesis; inflammation; ulcerative colitis; voluntary exercise