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

[1]  B. S. Mohammed,et al.  Relationship Between Body Fat Mass and Free Fatty Acid Kinetics in Men and Women , 2009, Obesity.

[2]  S. Wootton,et al.  Tissue-specific stable isotope measurements of postprandial lipid metabolism in familial combined hyperlipidaemia. , 2008, Atherosclerosis.

[3]  J. M. Aerts,et al.  Gender-related differences in the metabolic response to fasting. , 2007, The Journal of clinical endocrinology and metabolism.

[4]  John P H Wilding,et al.  The importance of free fatty acids in the development of Type 2 diabetes , 2007, Diabetic medicine : a journal of the British Diabetic Association.

[5]  B. S. Mohammed,et al.  Women produce fewer but triglyceride-richer very low-density lipoproteins than men. , 2007, The Journal of clinical endocrinology and metabolism.

[6]  Fredrik Karpe,et al.  Preferential Uptake of Dietary Fatty Acids in Adipose Tissue and Muscle in the Postprandial Period , 2007, Diabetes.

[7]  J. Tu,et al.  Relation between age and cardiovascular disease in men and women with diabetes compared with non-diabetic people: a population-based retrospective cohort study , 2006, The Lancet.

[8]  A. Häkkinen,et al.  Overproduction of large VLDL particles is driven by increased liver fat content in man , 2006, Diabetologia.

[9]  H. Barakat,et al.  Ketone body metabolism in lean and obese women. , 2005, Metabolism: clinical and experimental.

[10]  R. Pease,et al.  Mobilisation of triacylglycerol stores. , 2000, Biochimica et biophysica acta.

[11]  M. Laville,et al.  Effect of physiological concentrations of insulin and glucagon on the relationship between nonesterified fatty acids availability and ketone body production in humans. , 1991, Metabolism: clinical and experimental.

[12]  M. Hellerstein,et al.  Measurement of de novo hepatic lipogenesis in humans using stable isotopes. , 1991, The Journal of clinical investigation.

[13]  K. Frayn,et al.  Micro-method for preparing perchloric extracts of blood. , 1988, Clinical chemistry.

[14]  U. Keller,et al.  Fatty acid-independent inhibition of hepatic ketone body production by insulin in humans. , 1988, The American journal of physiology.

[15]  B. Beaufrère,et al.  Determination of human ketone body kinetics using stable-isotope labelled tracers , 1986, Diabetologia.

[16]  M. Haymond,et al.  Effects of free fatty acid availability, glucagon excess, and insulin deficiency on ketone body production in postabsorptive man. , 1983, The Journal of clinical investigation.

[17]  K. Alberti,et al.  Hormonal control of ketone body metabolism in the normal and diabetic state. , 1982, Clinics in endocrinology and metabolism.

[18]  D. Kipnis,et al.  Physiologic Mechanisms in the Development of Starvation Ketosis in Man , 1975, Diabetes.

[19]  S. Fineberg,et al.  Homeostasis during fasting. II. Hormone substrate differences between men and women. , 1973, The Journal of clinical endocrinology and metabolism.

[20]  R. Havel,et al.  Splanchnic metabolism of free fatty acids and production of triglycerides of very low density lipoproteins in normotriglyceridemic and hypertriglyceridemic humans. , 1970, The Journal of clinical investigation.

[21]  C. Cobelli,et al.  Ketone body kineticsin vivo using simultaneous administration of acetoacetate and 3-hydroxybutyrate labelled with stable isotopes , 2007, Acta diabetologia latina.

[22]  F. Karpe,et al.  The in vivo effects of the Pro12Ala PPARγ2 polymorphism on adipose tissue NEFA metabolism: the first use of the Oxford Biobank , 2005, Diabetologia.

[23]  S. Wootton,et al.  Conversion of alpha-linolenic acid to palmitic, palmitoleic, stearic and oleic acids in men and women. , 2003, Prostaglandins, leukotrienes, and essential fatty acids.

[24]  W. Clarke,et al.  Differences in circulating gluconeogenic substrates during short-term fasting in men, women, and children. , 1982, Metabolism: clinical and experimental.