Effect of Dietary Macronutrient Composition

Obesity Clinical Trial

Official title:

Effect of Dietary Macronutrient Composition on Liver Substrate Metabolism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01371396
• Other study ID #: 5RL-1DK081187
• Status: Completed
• Phase: N/A
• Start date: September 1, 2007
• Est. completion date: December 31, 2013

Study information

• Verified date: February 2019
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 31, 2013
• Est. primary completion date: December 31, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Metabolic Syndrome
• Metabolic Syndrome X
• Non-alcoholic Fatty Liver Disease
• Obesity

Intervention

Other:
• Low-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.
• Low-carbohydrate diet
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.

Locations

Country	Name	City	State
United States	Center for Human Nutrition	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (6)

Lambert JE, Parks EJ. Getting the label in: practical research strategies for tracing dietary fat. Int J Obes Suppl. 2012 Dec;2(Suppl 2):S43-50. doi: 10.1038/ijosup.2012.22. Epub 2012 Dec 11. Review. — View Citation

Lee JJ, Lambert JE, Hovhannisyan Y, Ramos-Roman MA, Trombold JR, Wagner DA, Parks EJ. Palmitoleic acid is elevated in fatty liver disease and reflects hepatic lipogenesis. Am J Clin Nutr. 2015 Jan;101(1):34-43. doi: 10.3945/ajcn.114.092262. Epub 2014 Nov — View Citation

Ramos-Roman MA, Sweetman L, Valdez MJ, Parks EJ. Postprandial changes in plasma acylcarnitine concentrations as markers of fatty acid flux in overweight and obesity. Metabolism. 2012 Feb;61(2):202-12. doi: 10.1016/j.metabol.2011.06.008. Epub 2011 Aug 5. — View Citation

Satapati S, Kucejova B, Duarte JA, Fletcher JA, Reynolds L, Sunny NE, He T, Nair LA, Livingston KA, Fu X, Merritt ME, Sherry AD, Malloy CR, Shelton JM, Lambert J, Parks EJ, Corbin I, Magnuson MA, Browning JD, Burgess SC. Mitochondrial metabolism mediates — View Citation

Shetty S, Ramos-Roman MA, Cho YR, Brown J, Plutzky J, Muise ES, Horton JD, Scherer PE, Parks EJ. Enhanced fatty acid flux triggered by adiponectin overexpression. Endocrinology. 2012 Jan;153(1):113-22. doi: 10.1210/en.2011-1339. Epub 2011 Nov 1. — View Citation

Sunny NE, Parks EJ, Browning JD, Burgess SC. Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease. Cell Metab. 2011 Dec 7;14(6):804-10. doi: 10.1016/j.cmet.2011.11.004. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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