Dietary Protein and Hepatic Fat Accumulation

Study Overview
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Brief Summary
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The objective of this study is to investigate the potential beneficial effect of increasing protein in the diet in order to decrease hepatic lipid accumulation on a high-fat diet. The investigators hypothesize that increasing protein in a high-fat diet suppresses lipid accumulation in the liver, and that changes in (hepatic) fat handling underlie this reduced lipid accumulation.

Official Title
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Influence of Increasing Dietary Protein on Hepatic Fat Accumulation and Postprandial Metabolism

Conditions
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Hepatic Fat Accumulation, Nonalcoholic Fatty Liver Disease

Intervention / Treatment
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* Other: dietary protein
* Other: low-protein


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy body mass index (BMI) 18-25 kg/ m2; stable dietary habits; physical activity levels. caucasian Exclusion Criteria: Unable or unwilling to comply with study procedures; not caucasian Unstable body weight (weight gain or loss > 3 kg in the past three months); Moderate intense physical activity (exercise) for more than 4 hours/week; (Chronic) disease which might influence the study outcomes e.g. diabetes mellitus or any other endocrine disorder, active cardiovascular disease, hepatic disease, renal disease, cancer; Family history of diabetes mellitus; Use of medication, except incidental use of paracetamol; Abuse of drugs; Alcohol consumption of more than 14 glasses per week; Participation in another biomedical study within 1 months prior to the first screening visit; Contraindications to MRI scanning. These contraindications include patients with one of the following conditions: Claustrophobia; Central nervous system aneurysm clips; Implanted neural stimulator; Implanted cardiac pacemaker or defibrillator; Cochlear implant; Ocular foreign body (e.g. metal shavings); Insulin pump; Metal shrapnel or bullet; Or metal containing corpora aliena in the eye of brains.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High fat diets<br>High-fat-Low-protein or High-fat-high-protein | Other: dietary protein<br>* in the low-protein group 13EN% of protein will be provided in the diet; in the high-protein 25EN% of protein will be provided<br>* Other names: diet;|
| Other: Control group<br>Low-protein-low-fat (according to healthy eating guidelines) | Other: low-protein<br>* The control group will get a diet which is according to healthy eating guidelines.<br>* Other names: diet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hepatic fat accumulation |  | baseline, 2 weeks, 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers of liver function/hepatic steatosis | Biomarkers of liver function/hepatic steatosis: ALT, AST, C-reactive protein | baseline, 2 weeks, 4 weeks | 
| Circulating cytokines | adiponectin, TNF-α | baseline, 2 weeks, 4 weeks | 
| Postprandial lipid metabolism | Postprandial lipid metabolism will be assessed by means of a meal challenge with the use of stable isotope tracer | 2 weeks, 4 weeks | 
| Glucose homeostasis | Glucose homeostasis will be assessed with the homeostatic model assessment (HOMA) index in fasting blood samples. In addition dynamic indexes will be determined from the meal challenge. | baseline, 2 weeks, 4 weeks | 
| Adipose tissue gene expression |  | 2 weeks, 4 weeks | 
| Peripheral blood mononuclear cells gene expression (PBMC's). |  | baseline, 2 weeks, 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic fat accumulation, Dietary protein, NAFLD