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- Title
Sex Differences in Insulin Sensitivity are Related to Muscle Tissue Acylcarnitine But Not Subcellular Lipid Distribution.
- Authors
Broussard, Josiane L.; Perreault, Leigh; Macias, Emily; Newsom, Sean A.; Harrison, Kathleen; Bui, Hai Hoang; Milligan, Paul; Roth, Kenneth D.; Nemkov, Travis; D'Alessandro, Angelo; Brozinick, Joseph T.; Bergman, Bryan C.
- Abstract
<bold>Objective: </bold>Sex differences in insulin sensitivity are present throughout the life-span, with men having a higher prevalence of insulin resistance and diabetes compared with women. Differences in lean mass, fat mass, and fat distribution-particularly ectopic fat-have all been postulated to contribute to the sexual dimorphism in diabetes risk. Emerging data suggest ectopic lipid composition and subcellular localization are most relevant; however, it is not known whether they explain sex differences in obesity-induced insulin resistance.<bold>Methods: </bold>To address this gap, this study evaluated insulin sensitivity and subcellular localization of intramuscular triacylglycerol, diacylglycerol, and sphingolipids as well as muscle acylcarnitines and serum lipidomics in people with obesity.<bold>Results: </bold>Insulin sensitivity was significantly lower in men (P < 0.05); however, no sex differences were found in localization of intramuscular triacylglycerol, diacylglycerol, or sphingolipids in skeletal muscle. In contrast, men had higher total muscle acylcarnitine (P < 0.05) and long-chain muscle acylcarnitine (P < 0.05), which were related to lower insulin sensitivity (r = -0.42, P < 0.05). Men also displayed higher serum ceramide (P = 0.05) and lysophosphatidylcholine (P < 0.01).<bold>Conclusions: </bold>These data reveal novel sex-specific associations between lipid species involved in the coupling of mitochondrial fatty acid transport, β-oxidation, and tricarboxylic acid cycle flux that may provide therapeutic targets to improve insulin sensitivity.
- Subjects
INSULIN sensitivity; KREBS cycle; DISEASE prevalence; LIPIDS; LEAN body mass
- Publication
Obesity (19307381), 2021, Vol 29, Issue 3, p550
- ISSN
1930-7381
- Publication type
journal article
- DOI
10.1002/oby.23106