Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar;29(3):550-561.
doi: 10.1002/oby.23106.

Sex Differences in Insulin Sensitivity are Related to Muscle Tissue Acylcarnitine But Not Subcellular Lipid Distribution

Josiane L Broussard  1   2 , Leigh Perreault  1 , Emily Macias  1 , Sean A Newsom  3 , Kathleen Harrison  1 , Hai Hoang Bui  4 , Paul Milligan  5 , Kenneth D Roth  4 , Travis Nemkov  1 , Angelo D'Alessandro  1 , Joseph T Brozinick  4 , Bryan C Bergman  1
Affiliations

Sex Differences in Insulin Sensitivity are Related to Muscle Tissue Acylcarnitine But Not Subcellular Lipid Distribution

Josiane L Broussard et al. Obesity (Silver Spring). 2021 Mar.

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.

PubMed Disclaimer

Conflict of interest statement

DECLARATION OF INTEREST

The authors declare no competing interests.

Figures

Figure 1.
Figure 1.. Hyperinsulinemic-euglycemic clamp measurements in men and women with obesity.
Hyperinsulinemic-euglycemic clamp measurements of insulin sensitivity (A), nonoxidative glucose disposal (B), percentage suppression of hepatic glucose production (C) and percentage suppression of free fatty acid (D) in men and women with obesity. Data are mean + SEM. *P < 0.05, analyzed with unpaired Students t tests.
Figure 2.
Figure 2.. Whole-cell skeletal muscle lipid content in men and women with obesity.
Whole-cell skeletal muscle content of total intramuscular triacylglycerol (IMTG) (A), diacylglycerol (DAG) isomers (B) and sphingolipids (C) in men and women with obesity. Data are mean + SEM. *P < 0.05, analyzed with unpaired Students t tests.
Figure 3.
Figure 3.. Subcellular lipid localization in skeletal muscle in men and women with obesity.
Data are shown for cytosolic, sarcolemmal, nuclear and mitochondrial/ER fractions of total triacylglycerol (A), 1,2-DAG (B), 1,3-DAG (C), 1,2-DAG + 1,3-DAG (D), ceramide (E); dihydroceramide (F), sphingomyelin (G), glucosylceramide (H) and lactosylceramide (I) in men and women with obesity. Data are mean + SEM. *P < 0.05, analyzed with unpaired Students t tests and corrected for multiple comparisons.
Figure 3.
Figure 3.. Subcellular lipid localization in skeletal muscle in men and women with obesity.
Data are shown for cytosolic, sarcolemmal, nuclear and mitochondrial/ER fractions of total triacylglycerol (A), 1,2-DAG (B), 1,3-DAG (C), 1,2-DAG + 1,3-DAG (D), ceramide (E); dihydroceramide (F), sphingomyelin (G), glucosylceramide (H) and lactosylceramide (I) in men and women with obesity. Data are mean + SEM. *P < 0.05, analyzed with unpaired Students t tests and corrected for multiple comparisons.
Figure 4.
Figure 4.. Acylcarnitine content in whole-cell skeletal muscle in men and women with obesity.
Whole-cell skeletal muscle content of total acylcarntine under basal (A, left) and insulin-stimulated (A, right panel) conditions. Specific long-chain acylcarnitine species under basal (B) and insulin-stimulated (C) conditions. Data are mean + SEM. *P < 0.05, analyzed with unpaired Students t tests and corrected for multiple comparisons.
Figure 4.
Figure 4.. Acylcarnitine content in whole-cell skeletal muscle in men and women with obesity.
Whole-cell skeletal muscle content of total acylcarntine under basal (A, left) and insulin-stimulated (A, right panel) conditions. Specific long-chain acylcarnitine species under basal (B) and insulin-stimulated (C) conditions. Data are mean + SEM. *P < 0.05, analyzed with unpaired Students t tests and corrected for multiple comparisons.
Figure 5.
Figure 5.. Serum lipids in men and women with obesity.
Data are shown for total serum ceramide (A), specific ceramide species (B), serum lysophosphatidylcholine (C), and individual lysophosphatidylcholine species (D) under basal conditions. Data are mean + SEM. *P < 0.05, analyzed with unpaired Students t tests and corrected for multiple comparisons.
Figure 5.
Figure 5.. Serum lipids in men and women with obesity.
Data are shown for total serum ceramide (A), specific ceramide species (B), serum lysophosphatidylcholine (C), and individual lysophosphatidylcholine species (D) under basal conditions. Data are mean + SEM. *P < 0.05, analyzed with unpaired Students t tests and corrected for multiple comparisons.
Figure 6.
Figure 6.. Relationship between insulin sensitivity and multiple factors in men and women with obesity.
*P < 0.05, analyzed by Pearson correlation.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Prevention, U.S.D.o.H.a.H.S.C.f.D.C.a., National Diabetes Statistics Report; Estimates of Diabetes and Its Burden in the United States. 2020.
    1. Clausen JO, et al., Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of the impact of gender, body fat, physical fitness, and life-style factors. J Clin Invest, 1996. 98(5): p. 1195–209. - PMC - PubMed
    1. Garaulet M, et al., Anthropometric, computed tomography and fat cell data in an obese population: relationship with insulin, leptin, tumor necrosis factor-alpha, sex hormone-binding globulin and sex hormones. Eur J Endocrinol, 2000. 143(5): p. 657–66. - PubMed
    1. Lundsgaard AM and Kiens B, Gender differences in skeletal muscle substrate metabolism - molecular mechanisms and insulin sensitivity. Front Endocrinol (Lausanne), 2014. 5: p. 195. - PMC - PubMed
    1. Rune A, et al., Evidence against a sexual dimorphism in glucose and fatty acid metabolism in skeletal muscle cultures from age-matched men and post-menopausal women. Acta Physiol (Oxf), 2009. 197(3): p. 207–15. - PubMed

Publication types

MeSH terms

LinkOut - more resources