Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose. Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle–triglyceride and –cholesterol significantly increased during fructose but not glucose consumption. In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose. These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults.
Kimber L. Stanhope ... Lars Berglund, Peter J. Havel
Proposed mechanisms underlying the differential effects of fructose and glucose consumption.
Hepatic glucose metabolism is regulated by phosphofructokinase, which is inhibited by ATP and citrate when energy status is high, thus limiting hepatic uptake of dietary glucose and production of DNL substrates. The hepatic metabolism of dietary fructose is independent of energy status, resulting in unregulated hepatic fructose uptake and increased lipogenesis. The resulting increased hepatic lipid decreases apoB degradation and increases production/secretion of VLDL-TG, mainly as TG-rich VLDL1 (
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