Metabolic Syndrome, Non-alcoholic Fatty Liver Disease, Obesity
Conditions
Keywords
Metabolic syndrome, Non-alcoholic fatty liver disease, Obesity Metabolism, Stable isotopes, Dietary weight loss
Brief summary
The purpose of this study is to understand why Hispanics who are overweight have a higher incidence of fatty liver disease.
Detailed description
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.
Interventions
OTHERLow-fat diet
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.
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.
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| de novo lipogenesis | Change from Baseline in fatty acid synthesis at 5 months | In vivo measurement is made of liver fatty acid synthesis using stable isotope administration and analysis of plasma samples by GS/MS |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dietary fatty acid clearance to liver | Change from Baseline in dietary fat clearance at 5 months | Using a dietary stable isotope we will quantitate fat absorption and recycling of fat through the liver. |
| Adipose fatty acid flux | Change from Baseline in adipose fat flux at 5 months | A stable isotope is infused and the rate of adipose fatty acid release is calculated after analyzing blood samples. |
Countries
United States
Outcome results
None listed