title: Hepatic steatosis development with four weeks of physical inactivity in previously active, hyperphagic OLETF rats.
abstract: Physical activity-induced prevention of hepatic steatosis is maintained during short-term (7-day) transitions to an inactive state; however, whether these protective effects are present under a longer duration of physical inactivity is largely unknown. Here, we sought to determine whether previous physical activity had protective effects on hepatic steatosis and metabolic health following 4 wk of physical inactivity. Four-week old, hyperphagic, male Otsuka Long-Evans Tokushima fatty (OLETF) rats were randomly assigned to either a sedentary group for 16 wk (OLETF-SED), given access to running wheels for 16 wk with wheels locked 5 h (OLETF-WL5hr) or given access to running wheels for 12 wk with wheels locked 4 wk (OLETF-WL4wk) prior to death. Four weeks of physical inactivity caused hepatic steatosis development, but liver triglycerides remained 60% lower than OLETF-SED (P < 0.01), and this was associated with only a partial loss in activity-induced improvements in body composition, serum lipids, and glycemic control. Total hepatic mitochondrial palmitate oxidation, citrate synthase, and β-HAD activity returned to SED levels following 4 wk of inactivity, whereas markers of fatty acid uptake and lipogenesis remained relatively suppressed following 4 wk of inactivity. In addition, 4 wk of inactivity caused a complete loss of activity-induced increases in serum IL-6 and reductions in regulated upon activation, normal T-cell expressed, and secreted (RANTES), and a partial loss in reductions in leptin, monocyte chemoattractant protein-1, and TNF-α. In conclusion, 4 wk of physical inactivity does not result in a complete loss in physical activity-induced benefits but does cause deterioration in the liver phenotype and overall metabolic health in hyperphagic OLETF rats.
authors: Research Service-Harry S. Truman Memorial Veterans Medical Center, University of Missouri, Columbia, MO 65212, USA.
authors: Melissa A
authors: MA
authors: Linden
authors: Grace M
authors: GM
authors: Meers
authors: Meghan L
authors: ML
authors: Ruebel
authors: Nathan T
authors: NT
authors: Jenkins
authors: Frank W
authors: FW
authors: Booth
authors: M Harold
authors: MH
authors: Laughlin
authors: Jamal A
authors: JA
authors: Ibdah
authors: John P
authors: JP
authors: Thyfault
authors: R Scott
authors: RS
authors: Rector
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D015502:Absorptiometry, Photon; D000222:Adaptation, Physiological / Q000502:physiology; D050154:Adiposity / Q000235:genetics / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D002950:Citrate (si)-Synthase / Q000378:metabolism; D018450:Disease Progression; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000473:pathology*; D006963:Hyperphagia / Q000235:genetics / Q000473:pathology*; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology; D008099:Liver / Q000473:pathology; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D010084:Oxidation-Reduction; D051381:Rats; D020334:Rats, Inbred OLETF; D012420:Running / Q000502:physiology
chemical_list: D005227:Fatty Acids; D015094:3-Hydroxyacyl CoA Dehydrogenases; D002950:Citrate (si)-Synthase
keywords: hepatic steatosis; mitochondrial function; nonalcoholic fatty liver disease; physical inactivity