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Relationships between Very Low-Density Lipoproteins–Ceramides, −Diacylglycerols,and –Triacylglycerols in Insulin-Resistant Men |
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| Authors: | Justine M. Mucinski Camila Manrique-Acevedo Takhar Kasumov Timothy J. Garrett Ayman Gaballah Elizabeth J. Parks |
| Affiliation: | 1. Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, 65211 USA;2. Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of Missouri Columbia School of Medicine, Columbia, MO, 65212 USA Dalton Cardiovascular Research Center, University of Missouri Columbia School of Medicine, Columbia, MO, 65212 USA Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, 65201 USA;3. Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, 44195 USA Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH, 44272 USA;4. Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, 32603 USA;5. Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO, 65212 USA |
| Abstract: | This short report describes the relationships between concentrations of ceramides (CER), diacylglycerols (DAG), triacylglycerols (TAG) in very low-density lipoproteins (VLDL) particles, and hepatic lipid accumulation. VLDL particles were isolated from male subjects (n = 12, mean ± SD, age 42.1 ± 5.4 years, BMI 37.4 ± 4.1 kg/m2, ALT 45 ± 21 U/L) and apolipoprotein B100 (apoB100), VLDL-TAG, -CER, and -DAG quantified. The contents of all three lipids were highly correlated with VLDL particle number (r ≥ 0.768, p ≤ 0.003). The molar quantity of VLDL-TAG was 3× that of DAG and 137× that of CER (14,053 ± 5714, 5004 ± 2714, and 105 ± 49 mol/mol apoB100, respectively). Reduced VLDL-CER concentrations were associated with both higher insulin levels (r = −0.645, p = 0.024) and intrahepatic-TAG (r = −0.670, p = 0.017). In fatty liver, the secretion of hepatic TAG, CER, and DAG may be suppressed and contribute to intrahepatic lipotoxicity. The mechanisms by which hepatic-CER and -DAG synthesis and assembly into VLDL is coordinately controlled with TAG will be important in understanding the emerging role of elevated CER contributing to cardiometabolic disease. |
| Keywords: | Ceramides Lipids Metabolic syndrome NAFLD VLDL |