title: Analysis of the liver lipidome reveals insights into the protective effect of exercise on high-fat diet-induced hepatosteatosis in mice.
abstract: The accumulation of lipid at ectopic sites, including the skeletal muscle and liver, is a common consequence of obesity and is associated with tissue-specific and whole body insulin resistance. Exercise is well known to improve insulin resistance by mechanisms not completely understood. We performed lipidomic profiling via mass spectrometry in liver and skeletal muscle samples from exercise-trained mice to decipher the lipid changes associated with exercise-induced improvements in whole body glucose metabolism. Obesity and insulin resistance were induced in C57BL/6J mice by high-fat feeding for 4 wk. Mice then underwent an exercise training program (treadmill running) 5 days/wk (Ex) for 4 wk or remained sedentary (Sed). Compared with Sed, Ex displayed improved (P < 0.01) whole body metabolism as measured via an oral glucose tolerance test. Deleterious lipid species such as diacylglycerol (P < 0.05) and cholesterol esters (P < 0.01) that accumulate with high-fat feeding were decreased in the liver of trained mice. Furthermore, the ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) (the PC/PE ratio), which is associated with membrane integrity and linked to hepatic disease progression, was increased by training (P < 0.05). These findings occurred without corresponding changes in the skeletal muscle lipidome. A concomitant decrease (P < 0.05) was observed for the fatty acid transporters CD36 and FATP4 in the liver, suggesting that exercise stimulates a coordinated reduction in fatty acid entry into hepatocytes. Given the important role of the liver in the regulation of whole body glucose homeostasis, hepatic lipid regression may be a key component by which exercise can improve metabolism.
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; and Department of Nutrition, Exercise, and Sports, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Andreas B
authors.initials: AB
authors.lastname: Jordy
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; and.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kraakman
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; and.
authors.forename: Tim
authors.initials: T
authors.lastname: Gardner
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; and.
authors.forename: Emma
authors.initials: E
authors.lastname: Estevez
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; and.
authors.forename: Helene L
authors.initials: HL
authors.lastname: Kammoun
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; and.
authors.forename: Jacqui M
authors.initials: JM
authors.lastname: Weir
authors.affiliation: Department of Nutrition, Exercise, and Sports, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Kiens
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; and.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Meikle
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; and.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Febbraio
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; and darren.henstridge@bakeridi.edu.au.
authors.forename: Darren C
authors.initials: DC
authors.lastname: Henstridge
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000494:pharmacology; D005234:Fatty Liver / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D018149:Glucose Intolerance / Q000209:etiology / Q000378:metabolism; D006946:Hyperinsulinism / Q000209:etiology / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D055442:Metabolome / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010805:Physical Conditioning, Animal / Q000502:physiology*
chemical_list: D004041:Dietary Fats
keywords: exercise; fatty acid transporters; hepatic steatosis; insulin resistance; lipids; skeletal muscle