Young women partition fatty acids towards ketone body production rather than VLDL-TAG synthesis, compared with young men.

Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
The British journal of nutrition (Impact Factor: 3.45). 01/2011; 105(6):857-65. DOI: 10.1017/S0007114510004472
Source: PubMed

ABSTRACT Before the menopause, women are relatively protected against CVD compared with men. The reasons for this sex difference are not completely understood, but hepatic fatty acid metabolism may play a role. The present study aimed to investigate the utilisation of plasma NEFA by the liver and to determine whether they are partitioned differently into ketone bodies and VLDL-TAG in healthy, lean young men and women. Volunteers were studied during a prolonged overnight fast (12-19 h) using an intravenous infusion of [U-¹³C]palmitate. After 12 h fasting, the women had a more advantageous metabolic profile with lower plasma glucose (P < 0·05) and TAG (P < 0·05) but higher plasma NEFA (P < 0·05) concentrations. Plasma 3-hydroxybutyrate (3-OHB) concentrations rose more in women than in men, and the transfer of ¹³C from [U-¹³C]palmitate to plasma [¹³C]3-OHB reached a plateau 6-7 h after the start of the infusion in women but was still increasing at 6 h in men. This implies a slower 3-OHB production rate and/or dilution by other precursor pools in men. In women, the high isotopic enrichment of plasma 3-OHB suggested that systemic plasma fatty acids were the major source of 3-OHB production. However, in men, this was not observed during the course of the study (P < 0·01). There were no sex differences for the incorporation of ¹³C into VLDL1- or VLDL2-TAG. The ability of young women to partition fatty acids towards ketone body production rather than VLDL-TAG may contribute to their more advantageous metabolic profile compared with young men.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We measured the incorporation of systemic free fatty acids (FFA) into circulating VLDL-TG under postabsorptive, postprandial, and walking conditions in humans. Fifty five men and 85 premenopausal women with BMI 18-24 (lean) and 27-36 (overweight/obese) kg/m(2) received an intravenous bolus injection of [1,1,2,3,3-(2)H(5)]glycerol (to measure VLDL-TG kinetics) and either [1-(14)C]palmitate or [9,10-(3)H]palmitate to determine the proportion of systemic FFA that is converted to VLDL-TG. Experiments started at 0630 h after a 12-h overnight fast. In the postabsorptive protocol, participants rested and remained fasted until 1330 h. In the postprandial protocol, volunteers ingested frequent portions of a fat-free smoothie. In the walking protocol, participants walked on a treadmill for 5.5 h at ∼3×resting energy expenditure. Approximately 7% of circulating FFA was converted into VLDL-TG. VLDL-TG secretion rates were not statistically different among protocols. Visceral fat mass was the only independent predictor of VLDL-TG secretion explaining 33-57% of the variance. The small proportion of systemic FFA that is converted to VLDL-TG can confound the expected relationship between plasma FFA concentration and VLDL-TG secretion rates. Regulation of VLDL-TG secretion is complex in that despite a broad spectrum of physiological FFA concentrations, VLDL-TG secretion rates did not vary based on different acute substrate availability.
    Diabetes 02/2013; · 7.90 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The mechanisms by which exercise reduces fasting plasma triglyceride (TG) concentrations in women and the effect of negative energy balance independent of muscular contraction are not known. PURPOSE: The aim of this study was to evaluate the effects of equivalent energy deficits induced by exercise or calorie restriction on basal very low-density lipoprotein (VLDL) TG metabolism in women. METHODS: Eleven healthy women (age: 23.5±2.7 years, BMI: 21.6±1.4 kg/m) underwent a stable isotopically labeled tracer infusion study to determine basal VLDL-TG kinetics after performing, in random order, three experimental trials on the previous day: i) a single exercise bout (brisk walking at 60% of peak oxygen consumption for 123±18 min, with a net energy expenditure of 2.06±0.39 MJ (∼500 kcal)), ii) dietary energy restriction of 2.10±0.41 MJ, and iii) a control day of isocaloric feeding and rest (zero energy balance). RESULTS: Fasting plasma VLDL-TG concentration was ∼30% lower after the exercise trial compared to the control trial (P<0.001), whereas no significant change was detected after the calorie restriction trial (P=0.297 vs control). Relative to the control condition, exercise increased the plasma clearance rate of VLDL-TG by 22% (P=0.001) and reduced hepatic VLDL-TG secretion rate by ∼17% (P=0.042), whereas hypocaloric diet had no effect on VLDL-TG kinetics (P>0.2). CONCLUSIONS: (i) Exercise-induced hypotriglyceridemia in women manifests through a different mechanism (increased clearance and decreased secretion of VLDL-TG) than that previously described in men (increased clearance of VLDL-TG only), and (ii) exercise affects TG homeostasis by eliciting changes in VLDL-TG kinetics that cannot be reproduced by an equivalent diet-induced energy deficit, indicating that these changes are independent of the exercise-induced negative energy balance but instead are specific to muscular contraction.
    Medicine and science in sports and exercise 10/2012; · 4.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Plasma free fatty acids (FFA) are major substrates for hepatic VLDL-triglycerides (VLDL-TG) production. In addition, it is a common belief that VLDL-TG production is a substrate driven process primarily determined by systemic FFA delivery. This review summarizes recent research of our understanding of the regulation of VLDL-TG production. Recent studies have shown that increasing FFA flux is not inevitably associated with increased VLDL-TG production. Exercise induced increase in FFA flux resulting in unchanged VLDL-TG production in lean patients as well as in obese patients with increased hepatic fat despite exercise reduced hepatic fat content. With respect to the other inseparable conditions of insulin resistance and hyperinsulinemia, recent studies demonstrate that increased hepatic VLDL-TG production precedes the insulin resistance-associated impairment of the regulation of hepatic glucose production, whereas isolated chronic hyperinsulinemia (insulinoma) was not associated with increased VLDL-TG production. Insulin has been shown to have acute potent temporary suppressing effect on VLDL-TG production and new data demonstrates that increased glucagon reduces VLDL-TG production. Finally, recent studies indicate that sex hormones, oestrogen and testosterone, have no or very modest impact on VLDL-TG production. Regulation of hepatic VLDL-TG production involves interplay between systemic FFA delivery, hormonal, and nutritional factors that act in concert with hepatic fatty acid handling to regulate short-term and long-term VLDL-TG production. The results of recent studies underscore that our current understanding of these relationships is complex and needs further research.
    Current opinion in lipidology 05/2012; 23(4):321-6. · 6.13 Impact Factor

Full-text (2 Sources)

Available from
May 27, 2014