The Effect of a High-fat vs. High-sugar Diet on Liver Fat Accumulation and Metabolism

Study Overview
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Brief Summary
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Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the world. It is currently unclear why fat starts to accumulate in the liver, although both the amount and type of food consumed have been implicated. The majority of studies that have investigated the effects of dietary fat or sugar on liver fat have fed volunteers excess calories, which are known to increase liver fat. The effect of specific dietary components, when consumed as part of a diet not containing excess calories, on liver fat accumulation remains unclear.

Detailed Description
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This research aims to investigate the role excessive consumption of specific macronutrients may play in the development of NAFLD. This will be achieved by subjecting participants to two specific dietary interventions (high-fat, low-carbohydrate and low-fat, high-carbohydrate) in a randomized, crossover research design. Liver fat content, and whole-body and hepatic fasting and postprandial lipid metabolism will be assessed before and after the specific dietary interventions.

Official Title
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The Effect of a High Fat Compared to a High Sugar Diet on Liver Fat Accumulation and Metabolism

Conditions
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Fat; Liver, NAFLD

Intervention / Treatment
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* Other: High-fat, low-carbohydrate
* Other: Low-fat, high-carbohydrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is willing and able to give informed consent for participation in the study. BMI >25 <35kg/m2 No medical condition or relevant drug therapy known to affect liver, lipid or glucose metabolism Exclusion Criteria: Age <30 or >65 years Body mass index <25 or >35kg/m2 A blood haemoglobin <120mg/dL Any metabolic condition or relevant drug therapy People who do not tolerate fructose Smoking History of alcoholism or a greater than recommended alcohol intake Pregnant or nursing mothers Women prescribed any contraceptive agent or device including oral contraceptives, hormone replacement therapy (HRT) or who have used these within the last 12 months History of severe claustrophobia Presence of metallic implants, pacemaker Haemorrhagic disorders Anticoagulant treatment

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 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: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomised crossover with washout period.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High-fat, low-carbohydrate diet<br>Dietary intervention: Participants will consume a diet that is rich in saturated fat (20% total energy) and low in free sugars for 4 weeks. This diet will include commonly eaten foods such as butter, cheese, and fatty meat products. Total fat intake in this intervention will be 40-45% total energy. | Other: High-fat, low-carbohydrate<br>* Dietary intervention: 4 week<br>|
| Active Comparator: Low-fat, high-carbohydrate diet<br>Dietary intervention: Participants will consume a diet that is low in saturated fat ( 5% total energy) and rich in free sugars (20% total energy).The diet will include commonly eaten food and drink such as sugar sweetened beverages, confectionery (e.g. fruit gums) and table sugar. | Other: Low-fat, high-carbohydrate<br>* Dietary intervention: 4 week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in liver fat content | Investigators will measure the change in liver fat content after each of the 4 week intervention diets by magnetic resonance imaging/spectroscopy (MRI/S). | Before, and within 7 days after completion of each dietary intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hepatic fatty acid partitioning | Investigators will utilise stable isotope tracer methodology to measure the contribution of newly synthesised fatty acids and dietary fatty acids to triglyceride production and oxidation pathways in the liver after each of the 4 week intervention diets. | Within 7 days after completion of each dietary intervention | 
| Change in plasma metabolite concentrations | Circulating concentrations of glucose, insulin, non-esterified fatty acids, and triglycerides will be measured biochemically using a clinical analyser after each of the 4 week intervention diets. | Before, and within 7 days after completion of each dietary intervention. | 
| Change in whole-body fatty acid oxidation | Investigators will utilise stable isotope tracer methodology to measure whole-body dietary fatty acid oxidation after each of the 4 week intervention diets. | Within 7 days after completion of each dietary intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NAFLD, Fat intake, Sugar intake