Effect of Dietary Macronutrient Composition

University of Texas Southwestern Medical Center24 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Metabolic Syndrome Non-alcoholic Fatty Liver Disease Obesity

Interventions

Low-fat dietOTHER

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.

Low-carbohydrate dietOTHER

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.

Eligibility

Sex: ALLMin age: 20 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (1)

Center for Human Nutrition

Dallas, Texas, United States

Outcomes

Primary Outcomes

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

Time frame: Change from Baseline in fatty acid synthesis at 5 months

Secondary Outcomes

Dietary fatty acid clearance to liver

Using a dietary stable isotope we will quantitate fat absorption and recycling of fat through the liver.

Time frame: 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.

Time frame: Change from Baseline in adipose fat flux at 5 months

Data from ClinicalTrials.gov

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