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

J Clin Endocrinol Metab. 2015 Jun;100(6):2434-42. doi: 10.1210/jc.2014-3678. Epub 2015 Mar 31.


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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism
  • Adiposity / drug effects
  • Adolescent
  • Adult
  • Aged
  • Body Weight / drug effects*
  • Dietary Carbohydrates / pharmacology*
  • Fructose / pharmacology*
  • Glucose / metabolism
  • Humans
  • Lipid Metabolism / drug effects
  • Lipogenesis / drug effects*
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Middle Aged
  • Young Adult


  • Dietary Carbohydrates
  • Fructose
  • Glucose