Effect of Fructose Overfeeding and Fish Oil Administration on Hepatic De Novo Lipogenesis and Insulin Sensitivity in Healthy Men

  1. David Faeh12,
  2. Kaori Minehira1,
  3. Jean-Marc Schwarz34,
  4. Raj Periasamy4,
  5. Seongsoo Park3 and
  6. Luc Tappy1
  1. 1Department of Physiology, University of Lausanne, Lausanne, Switzerland
  2. 2University Institute of Social and Preventive Medicine, Lausanne, Switzerland
  3. 3Department of Medicine, University of California at San Francisco, San Francisco, California
  4. 4Basic Science, Touro University, Mare lland, California
  1. Address correspondence and reprint requests to Prof. Luc Tappy, Département de physiologie, 7 rue du Bugnon, 1005 Lausanne, Switzerland. E-mail: luc.tappy{at}


High-fructose diet stimulates hepatic de novo lipogenesis (DNL) and causes hypertriglyceridemia and insulin resistance in rodents. Fructose-induced insulin resistance may be secondary to alterations of lipid metabolism. In contrast, fish oil supplementation decreases triglycerides and may improve insulin resistance. Therefore, we studied the effect of high-fructose diet and fish oil on DNL and VLDL triglycerides and their impact on insulin resistance. Seven normal men were studied on four occasions: after fish oil (7.2 g/day) for 28 days; a 6-day high-fructose diet (corresponding to an extra 25% of total calories); fish oil plus high-fructose diet; and control conditions. Following each condition, fasting fractional DNL and endogenous glucose production (EGP) were evaluated using [1-13C]sodium acetate and 6,6-2H2 glucose and a two-step hyperinsulinemic-euglycemic clamp was performed to assess insulin sensitivity. High-fructose diet significantly increased fasting glycemia (7 ± 2%), triglycerides (79 ± 22%), fractional DNL (sixfold), and EGP (14 ± 3%, all P < 0.05). It also impaired insulin-induced suppression of adipose tissue lipolysis and EGP (P < 0.05) but had no effect on whole- body insulin-mediated glucose disposal. Fish oil significantly decreased triglycerides (37%, P < 0.05) after high-fructose diet compared with high-fructose diet without fish oil and tended to reduce DNL but had no other significant effect. In conclusion, high-fructose diet induced dyslipidemia and hepatic and adipose tissue insulin resistance. Fish oil reversed dyslipidemia but not insulin resistance.


    • Accepted March 28, 2005.
    • Received January 25, 2005.
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