Adipose tissue triglyceride turnover, de novo lipogenesis, and cell proliferation in humans measured with 2H2O

The turnover of adipose tissue components ( lipids and cells) and the pathways of adipose lipid deposition have been difficult to measure in humans. We apply here a (H2O)-H-2 long-term labeling technique for concurrent measurement of adipose-triglyceride (TG) turnover, cell ( DNA) proliferation, and de novo lipogenesis (DNL). Healthy subjects drank (H2O)-H-2 ( 70 ml/day) for 5 - 9 wk. Subcutaneous adipose tissue aspirates were taken ( gluteal, thigh, and flank depots). Deuterium incorporation into TG glycerol ( representing all-source TG synthesis), TG palmitate ( representing DNL, by mass isotopomer distribution analysis), and DNA ( representing cell proliferation) was measured by gas chromatography-mass spectrometry. Subjects tolerated the protocol well, and body (H2O)-H-2 enrichments were stable. Mean TG-glycerol fractional synthesis was 0.12 (i.e., 12%) with a range of 0.03-0.32 after 5 wk and 0.20 ( range 0.08 - 0.49) after 9 wk ( TG half-life 200 - 270 days). Label decay measurements 5 - 8 mo after discontinuing (H2O)-H-2 gave similar turnover estimates. Net lipolysis ( TG turnover) was 50 - 60 g/day. DNL contribution to adipose-TG was 0.04 after 9 wk, representing similar to 20% of newly deposited TG. Cell proliferation was 0.10 - 0.17 after 9 wk (half-life 240 - 425 days). In summary, long-term (H2O)-H-2 administration to human subjects allows measurement of the dynamics of adipose tissue components. Turnover of all elements is slow, and DNL contributes similar to 20% of new TG.