Quantification of menstrual and diurnal periodicities in rates of cholesterol and fat synthesis in humans.

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 ace...

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Main Authors: D Faix, R Neese, C Kletke, S Wolden, D Cesar, M Coutlangus, CHL Shackleton, M K Hellerstein
Format: Article
Language:English
Published: Elsevier 1993-12-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520353487
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author D Faix
R Neese
C Kletke
S Wolden
D Cesar
M Coutlangus
CHL Shackleton
M K Hellerstein
author_facet D Faix
R Neese
C Kletke
S Wolden
D Cesar
M Coutlangus
CHL Shackleton
M K Hellerstein
author_sort D Faix
collection DOAJ
description 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.
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spelling doaj.art-6d13c4a6e74a4a59bbdafa28d346a2422022-12-21T20:44:13ZengElsevierJournal of Lipid Research0022-22751993-12-01341220632075Quantification of menstrual and diurnal periodicities in rates of cholesterol and fat synthesis in humans.D Faix0R Neese1C Kletke2S Wolden3D Cesar4M Coutlangus5CHL Shackleton6M K Hellerstein7Department of Nutritional Sciences, University of California, Berkeley, CA 94720.Department of Nutritional Sciences, University of California, Berkeley, CA 94720.Oakland Children’s Hospital Research Institute, Oakland, CA 94609Division of Endocrinology and Metabolism, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, 1001 Potrero Avenue, San Francisco, CA 94110Department of Nutritional Sciences, University of California, Berkeley, CA 94720.Department of Nutritional Sciences, University of California, Berkeley, CA 94720.Oakland Children’s Hospital Research Institute, Oakland, CA 94609To whom reprint requests should be addressed.; Department of Nutritional Sciences, University of California, Berkeley, CA 94720.; Division of Endocrinology and Metabolism, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, 1001 Potrero Avenue, San Francisco, CA 94110The 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.http://www.sciencedirect.com/science/article/pii/S0022227520353487mass isotopomerspolymerization biosynthesisde novo lipogenesisacetyl-coAlipogenesis in women
spellingShingle D Faix
R Neese
C Kletke
S Wolden
D Cesar
M Coutlangus
CHL Shackleton
M K Hellerstein
Quantification of menstrual and diurnal periodicities in rates of cholesterol and fat synthesis in humans.
Journal of Lipid Research
mass isotopomers
polymerization biosynthesis
de novo lipogenesis
acetyl-coA
lipogenesis in women
title Quantification of menstrual and diurnal periodicities in rates of cholesterol and fat synthesis in humans.
title_full Quantification of menstrual and diurnal periodicities in rates of cholesterol and fat synthesis in humans.
title_fullStr Quantification of menstrual and diurnal periodicities in rates of cholesterol and fat synthesis in humans.
title_full_unstemmed Quantification of menstrual and diurnal periodicities in rates of cholesterol and fat synthesis in humans.
title_short Quantification of menstrual and diurnal periodicities in rates of cholesterol and fat synthesis in humans.
title_sort quantification of menstrual and diurnal periodicities in rates of cholesterol and fat synthesis in humans
topic mass isotopomers
polymerization biosynthesis
de novo lipogenesis
acetyl-coA
lipogenesis in women
url http://www.sciencedirect.com/science/article/pii/S0022227520353487
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