Fructose-Induced Palmitate Synthesis in Overweight Subjects

Dietary fructose potently exacerbates the dyslipidemia associated with obesity, insulin resistance and accelerated atherosclerosis. In a randomized crossover outpatient study of 15 overweight adults, we will measure the increase over 4 hours in serum VLDL triglyceride palmitate made by the liver from each single oral dose of fructose (0.5 g/kg), fructose:glucose 1:1 (1 g/kg) or fructose:glucose 1:1 (2 g/kg). Our hypotheses are that the synthesis of palmitate from dietary fructose will be 1) greater when consumed with glucose and 2) show a dose-response. The lipogenic responses will be compared and correlated with markers of carbohydrate and lipid flux measured after fasting and post-fructose. The results will serve as a guide to the development of a new outpatient probe of the de novo lipogenic pathway in subjects who vary in their lipogenic response to oral fructose. These studies should ultimately yield valuable new information about the mechanisms linking dietary carbohydrate to elevated triglycerides, diabetes and cardiovascular disease.