De novo lipogenesis, lipid kinetics, and whole-body lipid balances in humans after acute alcohol consumption

Background: Acute alcohol intake is associated with changes in plasma lipid concentrations and whole-body lipid balances in humans. The quantitative r oles of hepatic de novo lipogenesis (DNL) and plasma acetate production in these changes have not been established, however. Objective: We used stable-isotope mass spectrometric methods with indirect calorimetry to establish the metabolic basis of changes in whole-body lipid balances in healthy men after consumption of 24 g alcohol. Design: Eight healthy subjects were studied and DNL (by mass-isotopomer dis tribution analysis), lipolysis (by dilution of [1,2,3,4-C-13(4)]palmitate a nd [H-2(5)]glycerol), conversion of alcohol to plasma acetate (by incorpora tion from [1-C-13(1)]ethanol), and plasma acetate flux (by dilution of [1-C -13(1)]acetate) were measured. Results: The fractional contribution from DNL to VLDL-triacylglycerol palmi tate rose after alcohol consumption from 2 +/- 1% to 30 +/- 8 %; neverthele ss, the absolute rate of DNL (0.8 g/6 h) represented <5% of the ingested al cohol dose; 77 +/- 13% of the alcohol cleared from plasma was converted dir ectly to acetate entering plasma. Acetate flux increased 2.5-fold after alc ohol consumption. Adipose release of nonesterified fatty acids into plasma decreased by 53% and whole-body lipid oxidation decreased by 73%. Conclusions: We conclude that the consumption of 24 g alcohol activates the hepatic DNL pathway modestly, but acetate produced in the liver and releas ed into plasma inhibits lipolysis, alters tissue fuel selection, and repres ents the major quantitative fate of ingested ethanol.