|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)|
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.
|Alternate Journal||Obesity (Silver Spring)|
|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