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

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

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Touro 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.



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.


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.


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.


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.


Short-term high-fructose intake was associated with increased DNL and liver fat in healthy men fed weight-maintaining diets.

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