No effect of menstrual cycle phase on basal very-low-density lipoprotein triglyceride and apolipoprotein B-100 kinetics

Abstract

(TG), increased total and LDL-cholesterol concentrations and decreased HDL-cholesterol concentration, is an important risk factor for cardiovascular disease. Premenopausal women have a less atherogenic plasma lipid profile and a lower risk of cardiovascular disease than men, but this female advantage disappears after menopause. This suggests that female sex steroids affect lipoprotein metabolism. The impact of variations in the availability of ovarian hormones during the menstrual cycle on lipoprotein metabolism is not known. We therefore investigated whether very-low-density lipoprotein (VLDL)-TG and VLDL-apolipoprotein B-100 (apoB-100) kinetics are different during the follicular (FP) and luteal phases (LP) of the menstrual cycle. We studied seven healthy, premenopausal women (age 27 Ϯ 2 yr, BMI 25 Ϯ 2 kg/m 2 ) once during FP and once during LP. We measured VLDL-TG, VLDL-apoB-100, and plasma free fatty acid (FFA) kinetics by using stable isotope-labeled tracers, VLDL subclass profile by nuclear magnetic resonance spectroscopy, whole body fat oxidation by indirect calorimetry, and the plasma concentrations of lipoprotein lipase (LPL) and hepatic lipase (HL) by ELISA. VLDL-TG and VLDLapoB-100 concentrations in plasma, VLDL-TG and VLDL-apoB-100 secretion rates and mean residence times, VLDL subclass distribution, FFA concentration and rate of appearance in plasma, whole body substrate oxidation, and LPL and HL concentrations in plasma were not different during the FP and the LP. We conclude that VLDL-TG and VLDL-apoB-100 metabolism is not affected by menstrual cycle phase. sex hormones; stable isotope; lipid DYSLIPIDEMIA, characterized by increased plasma triglyceride (TG), increased total and LDL-cholesterol, and reduced HDLcholesterol concentrations, is a major risk factor for cardiovascular disease (41). Premenopausal women have a lesser risk of developing cardiovascular disease than age-matched men, but the "female advantage" disappears after menopause (26). Differences in plasma lipid concentrations, particularly plasma TG concentration, between men and women and pre-and postmenopausal women are likely responsible for this phenomenon. The increase in cardiovascular disease risk resulting from a given rise in plasma TG concentration is more than twofold higher for women than for men (23). Premenopausal women have lower plasma TG concentration than men (55); this difference between the sexes is abolished after menopause because of an increase in plasma TG concentration that coincides with the onset of menopause (10). This suggests a beneficial effect of ovarian hormones on plasma TG metabolism. Findings from studies in postmenopausal women receiving hormone replacement therapy and premenopausal women taking hormonal contraceptives indicate that this is likely due to the lack of progesterone rather than estradiol.Hormone replacement therapy providing progestins alone to postmenopausal women decreases fasting plasma TG concentration, whereas estrogens increase fasting plasma TG concentration (19). Also, estroge...

Reproducibility of stable isotope-labeled tracer measures of VLDL-triglyceride and VLDL-apolipoprotein B-100 kinetics

“…This is very similar to the error estimates for VLDL-apoB-100 FTR and all other outcome variables in the present study in men. In addition, the day-to-day variability reported here in men is no less than the intraindividual variability for basal FFA, VLDL-TG, and VLDL-apoB-100 kinetics that we recently reported when studying premenopausal women once during the follicular phase and once during the luteal phase of the menstrual cycle (11). This finding strengthens our conclusion from the previous study that menstrual cycle Fig.…”

“…1) (7, 13, 28, 30). The total rate of VLDL-TG secretion (mmol/min), which represents the total amount of VLDL-TG secreted by the liver, was calculated by multiplying the FTR of VLDL-TG (pools/min) by the concentration of VLDL-TG in plasma (mmol/l) and the plasma volume (liters) (10,11,13); plasma volume was assumed to equal the VLDL-TG volume of distribution and was calculated as 0.055 l/kg fat-free mass (31). VLDL-TG plasma clearance rate (ml plasma/min) was calculated by dividing the VLDL-TG secretion rate by VLDL-TG concentration in plasma (i.e., FTR 3 plasma volume).…”

“…in a single session and require that subjects be studied on two different occasions several days or weeks apart. Owing to tracer cost and analytical burden, studies are usually conducted in small samples, typically 5-10 subjects (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The design and interpretation of these studies (particularly when dealing with negative findings) is difficult because there are no data available on the reliability of tracer measures of VLDL-TG and VLDL-apoB-100 kinetics.…”

“…The design and interpretation of these studies (particularly when dealing with negative findings) is difficult because there are no data available on the reliability of tracer measures of VLDL-TG and VLDL-apoB-100 kinetics. Therefore, we determined the reproducibility and degree of intraindividual variability of basal VLDL-TG, VLDL-apoB-100, and plasma FFA [a major precursor for VLDL-TG synthesis (10,11,20)] kinetics, assessed using stable isotope-labeled tracer methods. We then used this information to provide estimates of minimum detectable differences for any given sample size when assessing FFA, VLDL-TG, and VLDLapoB-100 metabolism with the methods described here.…”

Testosterone increases the muscle protein synthesis rate but does not affect very-low-density lipoprotein metabolism in obese premenopausal women

“…Sex differences in the plasma lipid profile have traditionally been attributed to differences in the sex hormone milieu; particularly the availability of estradiol, but also progesterone. However, we and others have shown that changes in ovarian steroid concentration during the normal menstrual cycle (26) and after menopause (6,23,50) are not associated with changes in very-low-density lipoprotein (VLDL)-TG and VLDL-apolipoprotein B-100 (apoB-100) kinetics and concentrations that are consistent with the observed sexual dimorphism in VLDL metabolism (53). Furthermore, oral estrogen preparations given to women and men increase total plasma TG and VLDL-TG concentrations due to increased hepatic VLDL-TG secretion, and transdermal administration of 17␤-estradiol, which better mimics normal endogenous estrogen delivery, does not affect or only modestly decreases (by Ͻ10%) plasma TG concentration (53).…”