Effect of a High-Fructose Weight-Maintaining Diet on Lipogenesis and Liver Fat

Context: Consumption of high-fructose diets promotes hepatic fatty acid synthesis (de novo lipogenesis [DNL]) and an atherogenic lipid profile. It is unclear whether these effects occur independent of positive energy balance and weight gain. Objectives: We compared the effects of a high-fructose, (25% of energy content) weight-maintaining diet to those of an isocaloric diet with the same macronutrient distribution but in which complex carbohydrate (CCHO) was substituted for fructose. Design, Setting, and Participants: Eight healthy men were studied as inpatients for consecutive 9-day periods. Stable isotope tracers were used to measure fractional hepatic DNL and endogenous glucose production (EGP) and its suppression during a euglycemic-hyperinsulinemic clamp. Liver fat was measured by magnetic resonance spectroscopy. Results: Weight remained stable. Regardless of the order in which the diets were fed, the high-fructose diet was associated with both higher DNL (average, 18.6 +/- 1.4% vs 11.0 +/- 1.4% for CCHO; P = .001) and higher liver fat (median, + 137% of CCHO; P = .016) in all participants. Fasting EGP and insulin-mediated glucose disposal did not differ significantly, but EGP during hyperinsulinemia was greater (0.60 +/- 0.07 vs 0.46 +/- 0.06 mg/kg/min; P = .013) with the high-fructose diet, suggesting blunted suppression of EGP. Conclusion: Short-term high-fructose intake was associated with increased DNL and liver fat in healthy men fed weight-maintaining diets.