TitleSex Differences in Insulin Sensitivity are Related to Muscle Tissue Acylcarnitine But Not Subcellular Lipid Distribution.
Publication TypeJournal Article
Year of Publication2021
AuthorsBroussard, JL, Perreault, L, Macias, E, Newsom, SA, Harrison, K, Bui, HHoang, Milligan, P, Roth, KD, Nemkov, T, D'Alessandro, A, Brozinick, JT, Bergman, BC
JournalObesity (Silver Spring)
Date Published03/2021

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 JournalObesity (Silver Spring)
PubMed ID33624435
Grant ListT32DK007658 / 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