Primary Outcome Measures:
- Hepatic de novo lipogenesis [ Time Frame: acute effect of dietary fructose (within 6 hours) ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Whole body lipid oxidation, glucose turnover, glycerol turnover, plasma substrates, hormone and energy expenditure (free fatty acid, glucose, lactate, beta-hydroxybutyrate, glycerol, VLDL- Triglycerides and insulin)
expression of key adipose genes [ Time Frame: acute effect of fructose (within 6 hours) ] [ Designated as safety issue: No ]
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