Skeletal Muscle Ceramides and Daily Fat Oxidation in Obesity and Diabetes

Overview

Journal Metabolism

Specialty Endocrinology

Date 2018 Jan 9

PMID 29307520

Citations 18

Authors

Nicholas T Broskey

Diana N Obanda

Jeffrey H Burton

William T Cefalu

Eric Ravussin

Affiliations

Soon will be listed here.

Abstract

Background/objectives: Ectopic accumulation of lipids in skeletal muscle and the formation of deleterious lipid intermediates is thought to contribute to the development of insulin resistance and type 2 diabetes mellitus (T2DM). Similarly, impaired fat oxidation (metabolic inflexibility) are predictors of weight gain and the development of T2DM; however, no study has investigated the relation between muscle ceramide accumulation and 24-hour macronutrient oxidation. The purpose of this study was to retrospectively explore the relationships between whole body fat oxidation and skeletal muscle ceramide accumulation in obese non-diabetic individuals (ND) and in people with obesity and T2DM.

Methods: Daily substrate oxidation was measured in a respiratory chamber and skeletal muscle ceramides were measured using liquid chromatographyelectrospray ionization tandem-mass spectrometry.

Results: After adjusting for sex, age, and BMI, no differences existed between the groups for fat oxidation or 24-h RQ. However, ceramides C18:1, C:20, C22, C24 and C24:1 were significantly higher in people with T2DM compared to ND whereas no differences existed for C16 and C18. Despite low amounts of muscle ceramides, fat oxidation rates were positively associated with ceramide species concentration in ND only. Our data suggests that ceramides do not interfere with whole-body fat oxidation in ND individuals whereas a persistent lipid oversupply results in excessive ceramide muscle accumulation in people with T2DM.

Citing Articles

Sarcopenia and cachexia: molecular mechanisms and therapeutic interventions.

Wang T, Zhou D, Hong Z MedComm (2020). 2025; 6(1):e70030.

PMID: 39764565 PMC: 11702502. DOI: 10.1002/mco2.70030.

Ceramides-Emerging Biomarkers of Lipotoxicity in Obesity, Diabetes, Cardiovascular Diseases, and Inflammation.

Delcheva G, Stefanova K, Stankova T Diseases. 2024; 12(9).

PMID: 39329864 PMC: 11443555. DOI: 10.3390/diseases12090195.

shRNA-mediated down-regulation of Acsl1 reverses skeletal muscle insulin resistance in obese C57BL6/J mice.

Roszczyc-Owsiejczuk K, Imierska M, Sokolowska E, Kuzmicki M, Pogodzinska K, Blachnio-Zabielska A PLoS One. 2024; 19(8):e0307802.

PMID: 39178212 PMC: 11343424. DOI: 10.1371/journal.pone.0307802.

Impact of Lipids on Insulin Resistance: Insights from Human and Animal Studies.

Elkanawati R, Sumiwi S, Levita J Drug Des Devel Ther. 2024; 18:3337-3360.

PMID: 39100221 PMC: 11298177. DOI: 10.2147/DDDT.S468147.

17α-Estradiol alleviates high-fat diet-induced inflammatory and metabolic dysfunction in skeletal muscle of male and female mice.

Bubak M, Mann S, Borowik A, Pranay A, Batushansky A, de Sousa Neto I Am J Physiol Endocrinol Metab. 2024; 326(3):E226-E244.

PMID: 38197793 PMC: 11193529. DOI: 10.1152/ajpendo.00215.2023.

References

Poitout V, Amyot J, Semache M, Zarrouki B, Hagman D, Fontes G . Glucolipotoxicity of the pancreatic beta cell. Biochim Biophys Acta. 2009; 1801(3):289-98. PMC: 2824006. DOI: 10.1016/j.bbalip.2009.08.006. View

Bajpeyi S, Myrland C, Covington J, Obanda D, Cefalu W, Smith S . Lipid in skeletal muscle myotubes is associated to the donors' insulin sensitivity and physical activity phenotypes. Obesity (Silver Spring). 2013; 22(2):426-34. PMC: 3883809. DOI: 10.1002/oby.20556. View

de la Maza M, Rodriguez J, Hirsch S, Leiva L, Barrera G, Bunout D . Skeletal muscle ceramide species in men with abdominal obesity. J Nutr Health Aging. 2015; 19(4):389-96. DOI: 10.1007/s12603-014-0548-7. View

Lexell J . Human aging, muscle mass, and fiber type composition. J Gerontol A Biol Sci Med Sci. 1995; 50 Spec No:11-6. DOI: 10.1093/gerona/50a.special_issue.11. View

Bergstrom J . Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest. 1975; 35(7):609-16. View

Chaurasia B, Summers S . Ceramides - Lipotoxic Inducers of Metabolic Disorders. Trends Endocrinol Metab. 2015; 26(10):538-550. DOI: 10.1016/j.tem.2015.07.006. View

Larson-Meyer D, Newcomer B, Heilbronn L, Volaufova J, Smith S, Alfonso A . Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function. Obesity (Silver Spring). 2008; 16(6):1355-62. PMC: 2748341. DOI: 10.1038/oby.2008.201. View

Bergman B, Brozinick J, Strauss A, Bacon S, Kerege A, Bui H . Serum sphingolipids: relationships to insulin sensitivity and changes with exercise in humans. Am J Physiol Endocrinol Metab. 2015; 309(4):E398-408. PMC: 4537923. DOI: 10.1152/ajpendo.00134.2015. View

Bartke N, Hannun Y . Bioactive sphingolipids: metabolism and function. J Lipid Res. 2008; 50 Suppl:S91-6. PMC: 2674734. DOI: 10.1194/jlr.R800080-JLR200. View

10.

Stuart C, McCurry M, Marino A, South M, Howell M, Layne A . Slow-twitch fiber proportion in skeletal muscle correlates with insulin responsiveness. J Clin Endocrinol Metab. 2013; 98(5):2027-36. PMC: 3644602. DOI: 10.1210/jc.2012-3876. View

11.

Kelpe C, Moore P, Parazzoli S, Wicksteed B, Rhodes C, Poitout V . Palmitate inhibition of insulin gene expression is mediated at the transcriptional level via ceramide synthesis. J Biol Chem. 2003; 278(32):30015-21. DOI: 10.1074/jbc.M302548200. View

12.

Larson-Meyer D, Smith S, Heilbronn L, Kelley D, Ravussin E, Newcomer B . Muscle-associated triglyceride measured by computed tomography and magnetic resonance spectroscopy. Obesity (Silver Spring). 2006; 14(1):73-87. PMC: 2677802. DOI: 10.1038/oby.2006.10. View

13.

McGarry J . Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes. 2002; 51(1):7-18. DOI: 10.2337/diabetes.51.1.7. View

14.

Randle P, Garland P, Hales C, Newsholme E . The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963; 1(7285):785-9. DOI: 10.1016/s0140-6736(63)91500-9. View

15.

Amati F, Dube J, Coen P, Stefanovic-Racic M, Toledo F, Goodpaster B . Physical inactivity and obesity underlie the insulin resistance of aging. Diabetes Care. 2009; 32(8):1547-9. PMC: 2713647. DOI: 10.2337/dc09-0267. View

16.

Coen P, Hames K, Leachman E, DeLany J, Ritov V, Menshikova E . Reduced skeletal muscle oxidative capacity and elevated ceramide but not diacylglycerol content in severe obesity. Obesity (Silver Spring). 2013; 21(11):2362-71. PMC: 4136513. DOI: 10.1002/oby.20381. View

17.

Coen P, Dube J, Amati F, Stefanovic-Racic M, Ferrell R, Toledo F . Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes concomitant with higher ceramide content. Diabetes. 2009; 59(1):80-8. PMC: 2797948. DOI: 10.2337/db09-0988. View

18.

WEIR J . New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol. 1949; 109(1-2):1-9. PMC: 1392602. DOI: 10.1113/jphysiol.1949.sp004363. View

19.

Obanda D, Hernandez A, Ribnicky D, Yu Y, Zhang X, Wang Z . Bioactives of Artemisia dracunculus L. mitigate the role of ceramides in attenuating insulin signaling in rat skeletal muscle cells. Diabetes. 2012; 61(3):597-605. PMC: 3282822. DOI: 10.2337/db11-0396. View

20.

Colberg S, Simoneau J, Thaete F, Kelley D . Skeletal muscle utilization of free fatty acids in women with visceral obesity. J Clin Invest. 1995; 95(4):1846-53. PMC: 295723. DOI: 10.1172/JCI117864. View