Acute Effect of Fructose on Lipid Metabolism and Gender Differences

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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Acute Effect of Fructose on Lipid Metabolism and Gender Differences

Conditions
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Lipid Metabolism

Intervention / Treatment
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* Dietary Supplement: fructose
* Dietary Supplement: Fructose


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: fructose<br>acute fructose administration | Dietary Supplement: fructose<br>* acute administration of 4 times 0.3g fructose/kg lean body mass<br>Dietary Supplement: Fructose<br>* acute administration of 4 times 0.3 g/kg fat-free mass oral fructose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatic de novo lipogenesis |  | acute effect of dietary fructose (within 6 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | acute effect of fructose (within 6 hours) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dietary fructose, plasma lipids, healthy humans, gender differences, hepatic de novo lipogenesis