It has been widely documented that fructose overfeeding increases plasma triglycerides and hepatic de novo lipogenesis, and impairs insulin sensitivity in healthy male volunteers. The effect of gender on the metabolic responses to fructose remains an important open question, however.

The objective of this study is to compare the effect of an acute oral fructose load on carbohydrate and lipid metabolism in healthy young males and females.

The study is aimed at comparing the effects of oral fructose on several specific metabolic pathways in males and females.Participants will receive an isoenergetic diet containing 55% carbohydrate, 15% protein and 35% lipids for three days prior to testing. After this period of controlled diet, they will be studied for 2 hours in the post-absorptive state (Time 0-120 min) and over a 6 hours period (Time 120-480 min) during which they will receive 4 loads of 0,30 g/kg fat free mass U-13C labelled fructose, at times 120, 180, 240, 300. Throughout the study, deuterated glucose and glycerol will be infused to monitor whole body glucose production and glycerol turnover.

The following parameters will be monitored in basal conditions and after the ingestion of the load of fructose:

• Glycerol turnover(glycerol 2H5)
• de novo lipogenesis (incorporation of 13C into palmitate of VLDLs)
• whole body energy expenditure and net substrate oxydation (indirect calorimetry)
• net fructose oxidation (breath 13CO2)
• glucose turnover: (6,6 2H2 Glucose)
• plasma glucose, free fatty acids, ketone bodies, lactate, insulin, triacylglycerol, total cholesterol, VLDL, LDL, and HDL subfractions

An adipose tissue (periumbilical subcutaneous) biopsy will be obtaine by needle aspiration under local anesthesia in fasting conditions (time 0 min) and after fructose (time 480 min) to assess the effects of fructose on adipose gene expression profile. Key genes involved in the regulation of carbohydrate (GLUT 4, hexokinase, PDH-kinase), lipid (FAT-CD36, FABP, acetylCoA carboxylase, malonyl-CoA decarboxylase, PPARg) and energy metabolism (PGC-1a, UCP2)will be monitored

Results obtained in males and females will be compared with two-way analysis of variance

Inclusion Criteria:

• Males and females
• Age 18-35
• Healthy
• Body mass indexes (BMI) between 19 and 25 kg/m2
• Informed consent obtained

Exclusion Criteria:

• Smokers
• Alcohol intake > 30g/day
• Drug abuse
• Diabetes mellitus