title: Quantification of menstrual and diurnal periodicities in rates of cholesterol and fat synthesis in humans.
abstract: 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.
authors.affiliation: Department of Nutritional Sciences, University of California, Berkeley 94720.
authors.forename: D
authors.initials: D
authors.lastname: Faix
authors.forename: R
authors.initials: R
authors.lastname: Neese
authors.forename: C
authors.initials: C
authors.lastname: Kletke
authors.forename: S
authors.initials: S
authors.lastname: Wolden
authors.forename: D
authors.initials: D
authors.lastname: Cesar
authors.forename: M
authors.initials: M
authors.lastname: Coutlangus
authors.forename: C H
authors.initials: CH
authors.lastname: Shackleton
authors.forename: M K
authors.initials: MK
authors.lastname: Hellerstein
mesh_terms: D000085:Acetates; D019342:Acetic Acid; D000105:Acetyl Coenzyme A / Q000378:metabolism; D002247:Carbon Isotopes; D002784:Cholesterol / Q000096:biosynthesis*; D002940:Circadian Rhythm; D005260:Female; D006801:Humans; D008055:Lipids / Q000096:biosynthesis*; D008079:Lipoproteins, VLDL / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism; D008297:Male; D008598:Menstruation / Q000502:physiology*; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D010507:Periodicity
chemical_list: D000085:Acetates; D002247:Carbon Isotopes; D008055:Lipids; D008079:Lipoproteins, VLDL; D010169:Palmitic Acids; D019308:Palmitic Acid; D000105:Acetyl Coenzyme A; D002784:Cholesterol; D019342:Acetic Acid