File(s) under permanent embargo
Analysis of the liver lipidome reveals insights into the protective effect of exercise on high-fat diet-induced hepatosteatosis in mice
journal contribution
posted on 2023-05-20, 04:45 authored by Jordy, AB, Kraakman, MJ, Gardner, T, Estevez, E, Kammoun, HL, Weir, JM, Kiens, B, Meikle, PJ, Febbraio, MA, Darren HenstridgeDarren HenstridgeThe 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.
History
Publication title
American Journal of Physiology: Endocrinology and MetabolismVolume
308Issue
9Pagination
E778-E791ISSN
0193-1849Department/School
School of Health SciencesPublisher
American Physiological SocietyPlace of publication
9650 Rockville Pike, Bethesda, USA, Md, 20814Rights statement
Copyright © 2015 the American Physiological SocietyRepository Status
- Restricted