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

Before the menopause, women are relatively protected against cardiovascular disease compared with men. The reasons for this are not completely understood but hepatic fatty acid metabolism may play a role. This study aimed to investigate the utilization of plasma non5 esterified fatty acids by the liver and to determine whether they are partitioned differently into ketone bodies and VLDL-triacylglycerol (TG) in healthy lean young men and women. Volunteers were studied during a prolonged overnight fast (12-19h) using an intravenous infusion of [U13 C]palmitate. After 12h fasting, the women had a more advantageous metabolic profile with lower plasma glucose (P < 0.05) and TG (P < 0.05) but higher plasma 10 NEFA (P < 0.05) concentrations. Plasma 3-hydroxybutyrate (3-OHB) concentrations rose more in women than men, and the transfer of 13 C from [U13 C]palmitate to plasma [ 13 C]3OHB reached a plateau 6-7h after the start of the infusion in women but was still increasing at 6h 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 15 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 13 C into VLDL1or VLDL2-TG. The ability of young women to partition fatty acids towards ketone body production rather than VLDL-TG, may contribute to their more advantageous metabolic profile compared to young men. 20