1900-P: Very Low-Density Lipoprotein Ceramides and Hepatic Lipid Accumulation

Abstract

Ceramides (CER) have been implicated, along with other lipotoxic lipids (diacylglycerols, triacylglycerols, TG) that play important roles in the development and progression of nonalcoholic fatty liver disease (NAFLD). No study to date has measured CER in very low-density lipoproteins (VLDL), along with other lipids from obese men with characteristics of the metabolic syndrome. Twelve subjects with metabolic abnormalities that put them at risk for NAFLD (mean±SD, age 42.1±5.4y, BMI 37.8±3.5 kg/m2, ALT 45±21 U/L) were studied. VLDL particles were isolated in the fasted state and CER measured via UPLC-MS/MS analysis. VLDL-apoB100 was measured by ELISA and intrahepatic triglycerides (IHTG) analyzed by MRS. Total VLDL-CER were positively correlated with both VLDL-TG (r = 0.572, P=0.004) and VLDL-apoB100 (r = 0.557, P=0.005). CER were negatively correlated with IHTG (r = -0.447, P= 0.02), as was VLDL-TG concentration (r = -0.551, P=0.006). These data suggest that CER and TG are packaged together in the liver and secreted on VLDL particles, and do not support the addition of CER to particles after they have been secreted. In these relatively healthy men, the data support the concept that liver lipid secretion is associated with a decreased risk for fat accumulation in the liver. An excretion of lipotoxic lipids like TG and CER in VLDL can protect the liver from excess lipid accumulation. Disclosure J.M. Mucinski: None.