British Journal of Nutrition

Metabolism and Metabolic Studies

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

Kyriakoula Marinoua1a2, Martin Adielsa3, Leanne Hodsona1, Keith N. Frayna1, Fredrik Karpea1 and Barbara A. Fieldinga1 c1

a1 Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK

a2 Department of Experimental Physiology, Athens University School of Medicine, Athens, Greece

a3 Wallenberg Laboratory, Sahlgrenska Center for Cardiovascular and Metabolic Research, Göteborg University, Göteborg, Sweden


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.

(Received June 24 2010)

(Revised September 30 2010)

(Accepted October 05 2010)

(Online publication January 21 2011)


c1 Corresponding author: Dr B. A. Fielding, email


Abbreviations: 3-OHB, 3-hydroxybutyrate; MPE, mole percent excess; Ra, rate of appearance; TTR, tracer:tracee ratio