Sex differences in lipid and glucose kinetics after ingestion of an acute oral fructose load

The increase in VLDL TAG concentration after ingestion of a high-fructose diet is more pronounced in men than in pre-menopausal women. We hypothesised that this may be due to a lower fructose-induced stimulation of de novo lipogenesis (DNL) in pre-menopausal women. To evaluate this hypothesis, nine healthy male and nine healthy female subjects were studied after ingestion of oral loads of fructose enriched with C-13(6) fructose. Incorporation of C-13 into breath CO2, plasma glucose and plasma VLDL palmitate was monitored to evaluate total fructose oxidation, gluconeogenesis and hepatic DNL, respectively. Substrate oxidation was assessed by indirect calorimetry. After C-13 fructose ingestion, 44.0 (SD 3.2)% of labelled carbons were recovered in plasma glucose in males v. 41.9 (SD 2.3)% in females (NS), and 42.9 (SD 3.7)% of labelled carbons were recovered in breath CO2 in males v. 43.0 (SD 4.5)% in females (NS), indicating similar gluconeogenesis from fructose and total fructose oxidation in males and females. The area under the curve for C-13 VLDL palmitate tracer-to-tracee ratio was four times lower in females (P<0.05), indicating a lower DNL. Furthermore, lipid oxidation was significantly suppressed in males (by 16.4 (SD 5.2), P<0.05), but it was not suppressed in females (-1.3 (SD 4.7) %). These results support the hypothesis that females may be protected against fructose-induced hypertriglyceridaemia because of a lower stimulation of DNL and a lower suppression of lipid oxidation.