Fructose Consumption and Metabolic Dysregulation

Study Overview
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Brief Summary
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High fructose intake is increasingly recognized as causative in development of prediabetes, metabolic syndrome and cardiovascular disease (CVD). The mechanisms underlying fructose-induced metabolic disturbances are unclear but are beginning to be unraveled. In contrast to metabolism of glucose, the breakdown of fructose leads to the generation of metabolites that stimulate hepatic de novo lipogenesis (DNL) and increased levels of both fasting and postprandial triglycerides. The key lipogenic transcription factor seems to be activated by fructose independently of insulin. However, it is still controversial whether fructose consumption increases DNL in man to the extent that it induces metabolic disturbances. Animal studies have shown that also the adipose tissue is responsive to fructose feeding fructose, and that high fructose-feeding induces insulin resistance and inflammation in the adipose tissue. The role of intestinal insulin resistance in fructose-induced dysmetabolism has not been studied in detail. The critical question is whether the metabolic disturbances are induced by calorie excess or by fructose per se.

Detailed Description
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Detailed description: Study subjects will participate to studies 1-4 before and 3 m after fructose diet: An oral fat load or a kinetic study with stable isotopes combined with an oral fat load. Determination of liver, subcutaneous and intra-abdominal fat. (Proton magnetic resonance spectroscopy ) Lipolytic enzymes, advanced lipid analysis, fat biopsies and genetic studies and gut microbiota profiling Oral glucose tolerance test and analysis of incretins and inflammatory biomarkers.

Official Title
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Fructose Consumption Aggravates Dysregulation of Postprandial Lipid Metabolism in Obese Hypertriglyceridemic Men With High Cardiometabolic Risk Profile and Associates With Liver Fat Deposition

Conditions
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Central Obesity, Hypertriglyceridemia

Intervention / Treatment
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* Dietary Supplement: Fructose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index 27-40 Waist > 96 cm Age 20-60 years Male Exclusion Criteria: Smoking Active health problems Contraindications to MRI scanning Bleeding tendency Abnormal liver or renal function tests Type 2 diabetes Evidence of metabolic or viral liver disease Alcohol intake > 21 units per week Chronic medication except ones needed for stable hypertension

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: After fructose feeding<br>After 3 month fructose diet 75 g/day | Dietary Supplement: Fructose<br>* 3 month fructose diet 75 g/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TG Plasma AUC | Before vs. after fructose challenge: Triglycerides (TG) plasma Area Under Curve (AUC) | Form the baseline (time point 1) to end of treatment at 3 months (time point 2) | 
| B48 Plasma AUC | Before vs. after fructose challenge: apolipoprotein (apo)B48 plasma Area Under Curve (AUC) | Form the baseline (time point 1) to end of treatment at 3 months (time point 2) | 
| TG Plasma iAUC | Before vs. after fructose challenge:Triglycerides (TG) plasma incremental Area Under Curve (iAUC) | Form the baseline (time point 1) to end of treatment at 3 months (time point 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DNL | Before vs. after fructose challenge: de novo lipogenesis (DNL) | Form the baseline (time point 1) to end of treatment at 3 months (time point 2) | 
| ApoC-III | Before vs. after fructose challenge: Apolipoprotein C-III (ApoC-III) | Form the baseline (time point 1) to end of treatment at 3 months (time point 2) | 
| β-OH Butyrate | Before vs. after fructose challenge: beta-OH butyrate (β-OH butyrate) | Form the baseline (time point 1) to end of treatment at 3 months (time point 2) | 
| Liver Fat | Before vs. after fructose challenge | Form the baseline (time point 1) to end of treatment at 3 months (time point 2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fructose, hypertriglyceridemia, postprandial lipids, de novo lipogenesis, stable isotopes