Glyceroneogenesis and the source of glycerol for hepatic triacylglycerol synthesis in humans

Glyceroneogenesis, i.e, the synthesis of the glycerol moiety of triacylglyc erol from pyruvate, has been suggested to be quantitatively important in bo th the liver and adipose tissue during fasting, However, the actual contrib ution of glyceroneogenesis to triacylglycerol synthesis has not been quanti fied in vivo in human studies. In the present study we have measured the co ntribution of glycerol and pyruvate to in vivo synthesis of hepatic triacyl glycerol in nonpregnant and pregnant women after an overnight fast. Five no npregnant women were administered [C-13(3)]glycerol tracer as prime constan t rate infusion, and the appearance of tracer in plasma glucose and triacyl glycerol was quantified using gas chromatography-mass spectrometry, The con tribution of pyruvate to hepatic triacylglycerol was quantified in nonpregn ant and pregnant women using the deuterium labeling of body water method, T he appearance of [H-2] in hydrogens on C-1 and C-3 of triacylglycerol was m easured following periodate oxidation of the glycerol isolated from hydroly zed triacylglycerol, After a 16-h fast, similar to6.1% of the plasma triacy lglycerol pool was derived from plasma glycerol, whereas 10 to 60% was deri ved from pyruvate in nonpregnant women and pregnant women early in gestatio n. Our data suggest that glyceroneogenesis from pyruvate is quantitatively a major contributor to plasma triacylglycerol synthesis and may be importan t for the regulation of very low density lipoprotein triacylglycerol produc tion. Our data also suggest that 3-glycerol phosphate is in rapid equilibri um with the triosephosphate pool, resulting in rapid labeling of the triose pool by the administered tracer glycerol, Because the rate of flux of trio sephosphate to glucose during fasting far exceeds that to triacylglycerol, more glycerol ends up in glucose than in triacylglycerol, Alternatively, th ere may be two distinct pools of 3-glycerol phosphate in the liver, one inv olved in generating triosephosphate from glycerol and the other involved in glyceride-glycerol synthesis.