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

J Lipid Res. 1993 Dec;34(12):2063-75.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetates
  • Acetic Acid
  • Acetyl Coenzyme A / metabolism
  • Carbon Isotopes
  • Cholesterol / biosynthesis*
  • Circadian Rhythm*
  • Female
  • Humans
  • Lipids / biosynthesis*
  • Lipoproteins, VLDL / biosynthesis
  • Liver / metabolism
  • Male
  • Menstruation / physiology*
  • Palmitic Acid
  • Palmitic Acids / metabolism
  • Periodicity*


  • Acetates
  • Carbon Isotopes
  • Lipids
  • Lipoproteins, VLDL
  • Palmitic Acids
  • Palmitic Acid
  • Acetyl Coenzyme A
  • Cholesterol
  • Acetic Acid