Measuring Lipogenesis and Cholesterol Synthesis in Humans with Deuterated Water: Use of Simple Gas Chromatographic/Mass Spectrometric Techniques

Lipogenesis and cholesterol synthesis can be studied by measuring the incorporation into fatty acids and cholesterol of deuterium from deuterated water. This has been previously achieved in human subjects using low levels of deuterium enrichment in plasma water, and thus in fatty acids and cholesterol. For the measurement of enrichment in lipids, this required the use of isotope ratio mass spectrometry, a tedious and time-consuming technique. It is shown that these measurements can be performed using the much simpler gas chromatography/mass spectrometry if higher, but always safe, deuterium enrichments in plasma water are obtained. Normal subjects ingested deuterated water in order to obtain stable enrichment in plasma water of 0.3% during a 60 h period. Enrichment in palmitate of plasma triglycerides (TG) plateaued (0.6-0.76%) whereas plasma cholesterol enrichment increased progressively 0.32 +/- 0.08% (12 h) to 0.78 +/- 0.18% (60 h). Endogenous synthesis was estimated to contribute, in post-absorptive subjects, 8-10% of the plasma TG pool and 3-5% of plasma free cholesterol pool. These data agree with results obtained previously using isotope ratio mass spectrometry. The present method will be useful for studies of normal and abnormal lipid metabolism in humans.