Effect of Dietary Macronutrient Composition

Study Overview
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Brief Summary
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The purpose of this study is to understand why Hispanics who are overweight have a higher incidence of fatty liver disease.

Detailed Description
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Obesity is a major factor driving the increased prevalence of hepatic steatosis in the US. However, little is known regarding the relationship between dietary intake and hepatic fat deposition or about the factors that promote loss of hepatic steatosis. Here, the investigators will determine how differences in dietary composition affect the development and regression of fatty liver. The investigators hypothesize that Hispanic subjects with metabolic syndrome will have higher liver fat synthesis rates compared to African American subjects. Using detailed in vivo, serial measurements of fuel metabolism (GC/MS and NMR) fatty acid metabolism will be measured in the liver and periphery. This will be the first study in which these two methodologies are used together to assess both glucose and fatty acid metabolism in the same subjects. Subjects will be tested before and after a dietary weight-loss intervention producing 6% body weight loss over 5 months. The specific aims are as follows: AIM 1: Determine the contribution of peripheral and dietary fat to liver-TG in Hispanics and African Americans with metabolic syndrome. Hypothesis: De novo lipogenesis will contribute to liver-TG in greater quantities compared to African Americans. AIM 2: Determine the effects of low-CHO and low-fat diets on liver fat regression. Hypothesis: Compared to a low-fat diet, a low-CHO diet will markedly decrease markers of inflammation coincident with greater improvements in insulin sensitivity as assessed by an intravenous glucose tolerance test.

Official Title
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Effect of Dietary Macronutrient Composition on Liver Substrate Metabolism

Conditions
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Obesity, Metabolic Syndrome, Non-alcoholic Fatty Liver Disease

Intervention / Treatment
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* Other: Low-fat diet
* Other: Low-carbohydrate diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Elevated serum ALT or metabolic syndrome African American or Hispanic Nondiabetic Men or women Smokers and nonsmokers Pre- and post-menopausal (+/- HRT) Stable body weight Age 20-65 years BMI between 25-45 kg/m2 Exclusion Criteria: Diabetes or Pregnancy Ethanol intake: males > 140 g/week, females > 70 g/week Chronic hepatitis B or chronic hepatitis C Hemochromatosis or Wilson's Disease Autoimmune hepatitis or primary biliary cirrhosis

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Hispanic subjects<br>Subjects will identify as Hispanic ethnicity. | Other: Low-fat diet<br>* The subject will consume a diet that is calorically restricted to cause at least a 6% body weight loss over 4 months. Fat will make up less than 30% of dietary energy.<br>Other: Low-carbohydrate diet<br>* The diet will be restricted in energy to cause at least a 6% loss of body weight over a 4 month period. Carbohydrate will provide less than 40% of total dietary energy.<br>|
| Other: African American subjects<br>Subjects will self-identify as African American in origin. | Other: Low-fat diet<br>* The subject will consume a diet that is calorically restricted to cause at least a 6% body weight loss over 4 months. Fat will make up less than 30% of dietary energy.<br>Other: Low-carbohydrate diet<br>* The diet will be restricted in energy to cause at least a 6% loss of body weight over a 4 month period. Carbohydrate will provide less than 40% of total dietary energy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| de novo lipogenesis | In vivo measurement is made of liver fatty acid synthesis using stable isotope administration and analysis of plasma samples by GS/MS | Change from Baseline in fatty acid synthesis at 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dietary fatty acid clearance to liver | Using a dietary stable isotope we will quantitate fat absorption and recycling of fat through the liver. | Change from Baseline in dietary fat clearance at 5 months | 
| Adipose fatty acid flux | A stable isotope is infused and the rate of adipose fatty acid release is calculated after analyzing blood samples. | Change from Baseline in adipose fat flux at 5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolic syndrome, Non-alcoholic fatty liver disease, Obesity Metabolism, Stable isotopes, Dietary weight loss