Effect of Dietary Macronutrient Composition
Effect of Dietary Macronutrient Composition on Liver Substrate Metabolism
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Actual)
Fase
- No aplica
Contactos y Ubicaciones
Ubicaciones de estudio
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Texas
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Dallas, Texas, Estados Unidos, 75390-9052
- Center for Human Nutrition
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación factorial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Otro: Hispanic subjects
Subjects will identify as Hispanic ethnicity.
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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.
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Otro: African American subjects
Subjects will self-identify as African American in origin.
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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.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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de novo lipogenesis
Periodo de tiempo: Change from Baseline in fatty acid synthesis at 5 months
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In vivo measurement is made of liver fatty acid synthesis using stable isotope administration and analysis of plasma samples by GS/MS
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Change from Baseline in fatty acid synthesis at 5 months
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Dietary fatty acid clearance to liver
Periodo de tiempo: Change from Baseline in dietary fat clearance at 5 months
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Using a dietary stable isotope we will quantitate fat absorption and recycling of fat through the liver.
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Change from Baseline in dietary fat clearance at 5 months
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Adipose fatty acid flux
Periodo de tiempo: Change from Baseline in adipose fat flux at 5 months
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A stable isotope is infused and the rate of adipose fatty acid release is calculated after analyzing blood samples.
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Change from Baseline in adipose fat flux at 5 months
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Elizabeth J Parks, PhD, UTSW Medical Center
Publicaciones y enlaces útiles
Publicaciones Generales
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 5RL-1DK081187
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