VLDL-triglyceride production after alcohol ingestion, studied using [2-13C1] glycerol

Abstract

We used [2-13C1]glycerol to characterize very low density lipoprotein (VLDL)-triglyceride kinetics and intrahepatic glycerol metabolism in normal men (n = 4) after alcohol (EtOH) ingestion. [2-13C1]glycerol was infused before and after the consumption of 48 g EtOH or a placebo. Three additional subjects also received [1-13C1]acetate in addition to the [2-13C1]glycerol with EtOH treatment. Incorporation of tracer into the glycerol or fatty acid moiety of VLDL-triglyceride was measured by gas chromatography–mass spectrometry and used to calculate VLDL-triglyceride production rates. Intrahepatic triose-phosphate enrichments were also calculated based on mass isotopomer distribution analysis of plasma glucose. There was no difference in VLDL-triglyceride production rates after 48 g EtOH (11.9 ± 3.7 mg/kg/h) or placebo (14.7 ± 3.3 mg/kg/h). The VLDL-triglyceride rate constants calculated by kinetic modeling using the glycerol and acetate tracers in the combined isotope infusion subjects were very closely correlated (r2 = 0.94). The peak VLDL-glycerol enrichments after EtOH were 22.5 ± 3.3% versus 7.6 ± 0.8% after placebo (P < 0.001), while intrahepatic triose-phosphate enrichments were 19.8 ± 1.3% and 13.1 ± 1.2% (P < 0.001), respectively. Moreover, the calculated asymptotic VLDL-glycerol enrichments (representing the hepatic α-glycerol phosphate enrichment) were significantly higher after EtOH than placebo. The higher ratio of VLDL-glycerol to triose-phosphate labeling after EtOH suggests a metabolic block at glycerol 3-phosphate dehydrogenase. We conclude that consumption of 48 g EtOH does not increase VLDL-triglyceride production in normal men but does cause accumulation of tracer in hepatic α-glycerol phosphate.—Siler, S. Q., R. A. Neese, E. J. Parks, and M. K. Hellerstein. VLDL-triglyceride production after alcohol ingestion studied using [2-13C1]glycerol. J. Lipid Res. 1998. 39: 2319–2328.

Keywords

• MIDA
• alcohol
• glycerol phosphate
• hypertriglyceridemia
• kinetic modeling