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Intramyocellular Ceramides: Subcellular Concentrations and Fractional De Novo Synthesis in Postabsorptive Humans

Year: 2017
Type: article
Abstract: We investigated the relationship between insulin resistance markers and subsarcolemmal (SS) and intramyofibrillar (IMF) ceramide concentrations, as well as the contribution of plasma palmitate (6.5-h infusion of [U-13C]palmitate) to intramyocellular ceramides. Seventy-six postabsorptive men and women had muscle biopsies 1.5, 6.5, and 24 h after starting the tracer infusion. Concentrations and enrichment of muscle ceramides were measured by liquid chromatography-tandem mass spectrometry. We found that HOMA of insulin resistance, plasma insulin, and triglyceride concentrations were positively correlated with SS C16:0 and C18:1 ceramide, but not SS C14:0-Cer, C20:0-Cer, C24:0-Cer, and C24:1-Cer concentrations; IMF ceramide concentrations were not correlated with any metabolic parameters. The fractional contribution of plasma palmitate to 16:0 ceramide was greater in SS than IMF (SS, 18.2% vs. IMF, 8.7%; P = 0.0006). Plasma insulin concentrations correlated positively with the fractional contribution of plasma palmitate to SS 16:0 ceramide. The fractional contribution of plasma palmitate to intramyocellular SS 16:0 ceramide was positively correlated with SS C16:0 ceramide concentrations (γ = 0.435; P = 0.002). We conclude that skeletal muscle SS ceramides, especially C16 to C18 chain lengths and the de novo synthesis of intramyocellular ceramide from plasma palmitate are associated with markers of insulin resistance.
Source: Diabetes
DOI: 10.2337/db17-0082
Language: English
Open Access status: bronze
Funders: Mayo Clinic, Mayo Foundation for Medical Education and Research, U.S. Public Health Service, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Mayo Clinic Building Interdisciplinary Research Careers in Women’s Health, Minnesota Obesity Center, G2270726550, G3421112638, G4088071324, FFA Metabolism in Different Types of Human Obesity, G5198777789, General Clinical Research Center, Diabetes and Metabolism, Regional Fatty Acid Metabolism In Humans, FFA Metabolism in Different Types of Human Obesity
OpenAlex ID: W2613259577
FWCI: 2.338
Cites: 37
Cited by: 46
Related to: 10