Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy men.
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.
Department of Physiology, University of Lausanne, Lausanne, Switzerland.
David
D
Faeh
Kaori
K
Minehira
Jean-Marc
JM
Schwarz
Raj
R
Periasamy
Raj
R
Periasami
Seongsu
S
Park
Park
P
Seongsu
Luc
L
Tappy
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005395:Fish Oils / Q000494:pharmacology*; D005632:Fructose / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007333:Insulin Resistance; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D012016:Reference Values; D014280:Triglycerides / Q000096:biosynthesis
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005395:Fish Oils; D007328:Insulin; D008055:Lipids; D014280:Triglycerides; D005632:Fructose