title: Voluntary wheel running attenuates lipopolysaccharide-induced liver inflammation in mice.
abstract: Sepsis induces an acute inflammatory response in the liver, which can lead to organ failure and death. Given the anti-inflammatory effects of exercise, we hypothesized that habitual physical activity could protect against acute sepsis-induced liver inflammation via mechanisms, including heat shock protein (HSP) 70/72. Male C57BL/6J mice (n = 80, ∼8 wk of age) engaged in physical activity via voluntary wheel running (VWR) or cage control (SED) for 10 wk. To induce sepsis, we injected (2 mg/kg ip) LPS or sterile saline (SAL), and liver was harvested 6 or 12 h later. VWR attenuated increases in body and epididymal adipose tissue mass, improved glucose tolerance, and increased liver protein content of PEPCK (P < 0.05). VWR attenuated increases in LPS-induced IL-6 signaling and mRNA expression of other inflammatory markers (TNF-α, chemokine C-C motif ligand 2, inducible nitric oxide synthase, IL-10, IL-1β) in the liver; however, this was not reflected at the whole body level, as systemic markers of inflammation were similar between SED and VWR. Insulin tolerance was greater in VWR compared with SED at 6 but not 12 h after LPS. The protective effect of VWR occurred in parallel with increases in the liver protein content of HSP70/72, a molecular chaperone that can protect against inflammatory challenges. This study provides novel evidence that physical activity protects against the inflammatory cascade induced by LPS in the liver and that these effects may be mediated via HSP70/72.
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Willem T
authors.initials: WT
authors.lastname: Peppler
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Zachary G
authors.initials: ZG
authors.lastname: Anderson
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Sutton
authors.affiliation: Departments of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri; and Department of Medicine, University of Missouri, Columbia, Missouri; and Research Service-Harry S. Truman Memorial VA Hospital, Columbia, Missouri.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Rector
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada, dcwright@uoguelph.ca.
authors.forename: David C
authors.initials: DC
authors.lastname: Wright
mesh_terms: D000818:Animals; D015415:Biomarkers; D001835:Body Weight / Q000502:physiology; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance; D007249:Inflammation / Q000139:chemically induced*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000502:physiology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D008070:Lipopolysaccharides; D005947:Glucose
keywords: exercise; inflammation; lipopolysaccharide; liver; physical activity