Relationships between Very Low-Density Lipoproteins-Ceramides, -Diacylglycerols, and -Triacylglycerols in Insulin-Resistant Men.

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.