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). 03/2011; 105(6):857-65. DOI: 10.1017/S0007114510004472
Source: PubMed


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.

Download full-text


Available from: Martin Adiels, Jan 07, 2014
  • Source
    • "Hepatic fatty acid oxidation has been shown to be upregulated in obese compared with nonobese individuals in the postabsorptive state (35); however, we are unaware of available data in the postprandial state. In addition, evidence of greater hepatic partitioning of fatty acids between oxidation and VLDL-TG production has been reported recently in postabsorptive lean women than in men (36). "
    [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.
    Full-text · Article · Feb 2013 · Diabetes
  • Source
    • "Indeed, recent studies demonstrated that women exhibit higher non-oxidative FFA disposal (i.e. esterification and storage as triglycerides) [129] and after an overnight fast, they preferentially partition FFA towards hepatic oxidation to ketone bodies, rather than incorporation into VLDL-TG [130]. FFA can also be shuttled back to adipose tissue through the direct FFA uptake pathway discussed above. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Women have more body fat than men, but in contrast to the deleterious metabolic consequences of the central obesity typical of men, the pear-shaped body fat distribution of many women is associated with lower cardiometabolic risk. To understand the mechanisms regulating adiposity and adipose tissue distribution in men and women, significant research attention has focused on comparing adipocyte morphological and metabolic properties, as well as the capacity of preadipocytes derived from different depots for proliferation and differentiation. Available evidence points to possible intrinsic, cell autonomous differences in preadipocytes and adipocytes, as well as modulatory roles for sex steroids, the microenvironment within each adipose tissue, and developmental factors. Gluteal-femoral adipose tissues of women may simply provide a safe lipid reservoir for excess energy, or they may directly regulate systemic metabolism via release of metabolic products or adipokines. We provide a brief overview of the relationship of fat distribution to metabolic health in men and women, and then focus on mechanisms underlying sex differences in adipose tissue biology.
    Full-text · Article · May 2012 · Biology of Sex Differences
  • Source

    Preview · Thesis · Jan 2011
Show more