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.

Inclusion Criteria:

• Males and females, 18-75 years of age
• Body mass index (BMI) 25-35 and within 10% of maximum weight
• Willing and able to stop fish oil, psyllium, other non-prescribed vitamins/supplements for 1 week prior to study until completion of study
• Willing to not drink alcohol for 24 h before each day of blood sampling

Exclusion Criteria:

• Diabetes or other endocrine disorder, hepatitis or other liver disorder, HIV, or autoimmune disease
• Medication(s) known to affect lipids, including hormonal contraceptives
• Recent acute illness
• Gastrointestinal disease resulting in significant GI dysfunction or malabsorption
• History of fasting TG >800 mg/dl
• History of ethanol abuse (current intake >2 drinks/d) or illicit drugs
• History of severe psychiatric illness
• If female, pregnant or breastfeeding
• Participation in an investigational drug study within one month of screening
• Unusual diet or extreme level of physical activity
• Have any other condition, which in the opinion of the investigator, should prohibit the participation in the study