Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: another paradox in endurance-trained athletes?

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Serval ID
serval:BIB_F542888BDF3E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: another paradox in endurance-trained athletes?
Journal
Diabetes
Author(s)
Amati F., Dubé J.J., Alvarez-Carnero E., Edreira M.M., Chomentowski P., Coen P.M., Switzer G.E., Bickel P.E., Stefanovic-Racic M., Toledo F.G., Goodpaster B.H.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Publication state
Published
Issued date
2011
Volume
60
Number
10
Pages
2588-2597
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural Publication Status: ppublish
Abstract
OBJECTIVE-Chronic exercise and obesity both increase intra-myocellular triglycerides (IMTGs) despite having opposing effects on insulin sensitivity. We hypothesized that chronically exercise-trained muscle would be characterized by lower skeletal muscle diacylglycerols (DAGs) and ceramides despite higher IMTGs and would account for its higher insulin sensitivity. We also hypothesized that the expression of key skeletal muscle proteins involved in lipid droplet hydrolysis, DAG formation, and fatty-acid partitioning and oxidation would be associated with the lipotoxic phenotype.RESEARCH DESIGN AND METHODS-A total of 14 normal-weight, endurance-trained athletes (NWA group) and 7 normal-weight sedentary (NWS group) and 21 obese sedentary (OBS group) volunteers were studied. Insulin sensitivity was assessed by glucose clamps. IMTGs, DAGs, ceramides, and protein expression were measured in muscle biopsies.RESULTS-DAG content in the NWA group was approximately twofold higher than in the OBS group and similar to 50% higher than in the NWS group, corresponding to higher insulin sensitivity. While certain DAG moieties clearly were associated with better insulin sensitivity, other species were not. Ceramide content was higher in insulin-resistant obese muscle. The expression of OXPAT/perilipin-5, adipose triglyceride lipase, and stearoyl-CoA desaturase protein was higher in the NWA group, corresponding to a higher mitochondrial content, proportion of type 1 myocytes, DAGs, and insulin sensitivity.CONCLUSIONS-Total myocellular DAGs were markedly higher in highly trained athletes, corresponding with higher insulin sensitivity, and suggest a more complex role for DAGs in insulin action. Our data also provide additional evidence in humans linking ceramides to insulin resistance. Finally, this study provides novel evidence supporting a role for specific skeletal muscle proteins involved in intramyocellular lipids, mitochondrial oxidative capacity, and insulin resistance. Diabetes 60:2588-2597, 2011
Pubmed
Web of science
Open Access
Yes
Funding(s)
Swiss National Science Foundation / Careers / PZ00P3-126339
Create date
17/11/2011 10:40
Last modification date
20/01/2020 7:20
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