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

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-C-13] 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 C-13 from [U-(13) C]palmitate to plasma [C-13]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 C-13 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.