Title | Sex Differences in Insulin Sensitivity are Related to Muscle Tissue Acylcarnitine But Not Subcellular Lipid Distribution. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Broussard, JL, Perreault, L, Macias, E, Newsom, SA, Harrison, K, Bui, HHoang, Milligan, P, Roth, KD, Nemkov, T, D'Alessandro, A, Brozinick, JT, Bergman, BC |
Journal | Obesity (Silver Spring) |
Volume | 29 |
Issue | 3 |
Pagination | 550-561 |
Date Published | 03/2021 |
ISSN | 1930-739X |
Abstract | 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. |
DOI | 10.1002/oby.23106 |
Alternate Journal | Obesity (Silver Spring) |
PubMed ID | 33624435 |
Grant List | T32DK007658 / DK / NIDDK NIH HHS / United States RR-00036 / / National Institutes of Health General Clinical Research Center / Seed grant / / The Center for Women's Health Research at the University of Colorado Anschutz Medical Campus / K01DK110138 / DK / NIDDK NIH HHS / United States R01DK089170 / DK / NIDDK NIH HHS / United States P30DK048520 / DK / NIDDK NIH HHS / United States |