Clinical trial NCT01371396: Effect of Dietary Macronutrient Composition
Official title: Effect of Dietary Macronutrient Composition on Liver Substrate Metabolism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome
Non-alcoholic Fatty Liver Disease
Obesity
Keywords: Metabolic syndrome
Non-alcoholic fatty liver disease
Obesity Metabolism
Stable isotopes
Dietary weight loss
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2011-06-10
Enrollment: 24
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: de novo lipogenesis
timeFrame: Change from Baseline in fatty acid synthesis at 5 months
Secondary outcomes:
measure: Dietary fatty acid clearance to liver
timeFrame: Change from Baseline in dietary fat clearance at 5 months
measure: Adipose fatty acid flux
timeFrame: Change from Baseline in adipose fat flux at 5 months
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Center for Human Nutrition
state: Texas
Study officials:
affiliation: UTSW Medical Center
name: Elizabeth J Parks, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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 oxidative stress and inflammation in fatty liver. J Clin Invest. 2016 Apr 1;126(4):1605. doi: 10.1172/JCI86695. Epub 2016 Apr 1. No abstract available.
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 19.
citation: 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.
citation: Ramos-Roman MA, Lapidot SA, Phair RD, Parks EJ. Insulin activation of plasma nonesterified fatty acid uptake in metabolic syndrome. Arterioscler Thromb Vasc Biol. 2012 Aug;32(8):1799-808. doi: 10.1161/ATVBAHA.112.250019. Epub 2012 Jun 21.