TY - JOUR T1 - Effect of Fructose Overfeeding and Fish Oil Administration on Hepatic De Novo Lipogenesis and Insulin Sensitivity in Healthy Men JF - Diabetes JO - Diabetes SP - 1907 LP - 1913 DO - 10.2337/diabetes.54.7.1907 VL - 54 IS - 7 AU - Faeh, David AU - Minehira, Kaori AU - Schwarz, Jean-Marc AU - Periasamy, Raj AU - Park, Seongsoo AU - Tappy, Luc Y1 - 2005/07/01 UR - http://diabetes.diabetesjournals.org/content/54/7/1907.abstract N2 - 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 &lt; 0.05). It also impaired insulin-induced suppression of adipose tissue lipolysis and EGP (P &lt; 0.05) but had no effect on whole- body insulin-mediated glucose disposal. Fish oil significantly decreased triglycerides (37%, P &lt; 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. ER -