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Journal of Lipid Research, Vol 34, 2063-2075, Copyright © 1993 by Lipid Research, Inc.
D Faix, R Neese, C Kletke, S Wolden, D Cesar, M Coutlangus, CH Shackleton and MK Hellerstein
The mass isotopomer distribution analysis (MIDA) technique is applied here
in men and menstruating women to quantify periodicities in the biosynthesis
of serum cholesterol and very low density lipoprotein (VLDL)-palmitate. The
isotopic enrichment of the true biosynthetic precursor (intracellular
acetyl-CoA) during oral or intravenous administration of sodium[1-13C]- or
[2-13C]acetate was calculated from mass isotopomer fractional abundances in
free cholesterol and VLDL- palmitate, determined by gas chromatography-mass
spectrometry (GC-MS). To convert fractional into absolute cholesterol
synthesis rates, decay rate constants of plasma cholesterol were determined
from the die-away curves of endogenously labeled high-mass isotopomers.
Oral [13C]acetate was a 3-4 times more efficient means of labeling the
precursor pool for VLDL-palmitate than was intravenous [13C]acetate,
consistent with a splanchnic site of VLDL-fatty acid synthesis, whereas the
precursor for free cholesterol had an intermediate enrichment, suggesting a
contribution from extra-splanchnic tissues as well. Endogenous synthesis of
serum cholesterol was 8-11 mg/kg per day (an estimated 65- 75% of input
into serum cholesterol); it was 1.5- to 3-fold higher at night than during
the day (37-49 mg/h at night compared to 9-23 mg/h during the day) and did
not vary over the menstrual cycle (608-697 mg/day). In contrast, endogenous
synthesis of fatty acids made a relatively minor contribution to body fat
pools (1/10-1/20) of input into VLDL-palmitate) compared to dietary fat
intake; it was greater in the day-time, and was influenced by menstrual
cycle (3-fold elevated in the follicular phase compared to the luteal
phase), and body composition (higher in obese men than normal weight men,
r2 = 0.59 for lipogenesis vs. body mass index). Factors responsible for
periodicities in endogenous lipid synthesis can be studied in humans using
this approach.
ARTICLES
Quantification of menstrual and diurnal periodicities in rates of cholesterol and fat synthesis in humans
Department of Nutritional Sciences, University of California, Berkeley 94720.
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