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1 Department of Nutritional Sciences & Toxicology, University of California at Berkeley, Berkeley, CA, USA
2 San Francisco General Hospital, Department of Medicine, Division of Endocrinology and Metabolism, University of California at San Francisco, San Francisco, CA, USA
3 Department of Nutritional Sciences & Toxicology, University of California at Berkeley, Berkeley, CA, USA; San Francisco General Hospital, Department of Medicine, Division of Endocrinology and Metabolism, University of California at San Francisco, San Francisco, CA, USA
* To whom correspondence should be addressed. E-mail: march{at}nature.berkeley.edu.
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 heavy water (2H2O) long-term labeling technique for concurrent measurement of adipose-triglyceride (TG) turnover, cell (DNA) proliferation and de novo lipogenesis (DNL). Healthy subjects drank 2H2O (70 ml/day) for 5-9 weeks. 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) were measured by gas chromatography/mass spectrometry. Subjects tolerated the protocol well and body 2H2O enrichments were stable. Mean TG-glycerol fractional synthesis was 12% (range 3-32%) after 5 weeks and 20% (range 8-49%) after 9 weeks (TG half-life 200-270d). Die-away measurements 5-8 months after discontinuing 2H2O gave similar turnover estimates. Net lipolysis (TG turnover) was 50-60 g/d. DNL contribution to adipose-TG was 4% after 9 weeks, representing about 20% of newly deposited TG. Cell proliferation was 10-17% after 9 weeks (t1/2 240-425 days). In summary, long-term 2H2O administration to human subjects allows measurement of the dynamics of adipose tissue components. Turnover of all elements is slow and DNL contributes about 20% of new TG.
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