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Analysis of the liver lipidome reveals insights into the protective effect of exercise on high-fat diet-induced hepatosteatosis in mice


Jordy, AB and Kraakman, MJ and Gardner, T and Estevez, E and Kammoun, HL and Weir, JM and Kiens, B and Meikle, PJ and Febbraio, MA and Henstridge, DC, Analysis of the liver lipidome reveals insights into the protective effect of exercise on high-fat diet-induced hepatosteatosis in mice, American Journal of Physiology: Endocrinology and Metabolism, 308, (9) pp. E778-E791. ISSN 0193-1849 (2015) [Refereed Article]

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Copyright 2015 the American Physiological Society

DOI: doi:10.1152/ajpendo.00547.2014


The accumulation of lipid at ectopic sites, including the skeletal muscle and liver, is a common consequence of obesity and is associated with tissuespecific 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.

Item Details

Item Type:Refereed Article
Keywords:exercise, fatty acid transporters, hepatic steatosis, insulin resistance, lipids, skeletal muscle, 3 hydroxyacyl coenzyme A dehydrogenase, cholesterol ester, diacylglycerol, fatty acid transporter, lipidome, phosphatidylcholine, triacylglycerol
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell metabolism
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Henstridge, DC (Mr Darren Henstridge)
ID Code:133355
Year Published:2015
Web of Science® Times Cited:30
Deposited By:Health Sciences
Deposited On:2019-06-24
Last Modified:2019-08-22

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