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Sex Differences in Insulin Sensitivity are Related to Muscle Tissue Acylcarnitine But Not Subcellular Lipid Distribution
Author(s) -
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.
Publication year - 2021
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.23106
Subject(s) - medicine , endocrinology , insulin resistance , skeletal muscle , insulin , sphingolipid , biology , lipid metabolism , diabetes mellitus , biochemistry
Objective 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. Methods 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. Results 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). Conclusions 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.