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Updated: Apr 15, 2026
Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
Published on: March 11, 2017
Effect of a High-Fructose Weight-Maintaining Diet on Lipogenesis and Liver Fat
Jean-Marc Schwarz1, Susan M Noworolski1, Michael J Wen1
1Touro University (J.M.S., A.D., J.L.P., N.B.), Vallejo, California 94594; Department of Medicine (J.M.S., M.E.W., T.P.B., M.N.R., M.S., K.M.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology (J.M.S., M.J.W., M.E.W., V.W.T., M.N.R., M.S., K.M.), San Francisco General Hospital, San Francisco, California 94110; Department of Radiology and Biomedical Imaging (S.M.N.), University of California, San Francisco, San Francisco, California 94143; UCSF Clinical and Translational Science Institute Clinical Research Center (L.A.H., V.W.T.), San Francisco, California 94143; and The Gladstone Institute of Cardiovascular Disease (T.P.B.), San Francisco, California 94158.
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.
