Hepatic De Novo Lipogenesis (DNL)in the Pathogenesis of Hepatic Steatosis in Obese Youth
Nonalcoholic Fatty Liver Disease (NAFLD) is becoming the most common cause of liver disease in pediatrics, but little is known about its pathophysiology in children. While studies in obese adults with hepatic steatosis have described an increased hepatic de novo lipogenesis (DNL) depending on the diet, there are no studies exploring the mechanisms by which excess hepatic triglycerides increases in obese youths, thus explaining the accompanying dyslipidemia and the metabolic syndrome. The central hypothesis of this study is that hepatic conversion of carbohydrates to lipid (DNL) is enhanced and associated with accumulation of excess liver fat, dyslipidemia and hepatic insulin resistance in obese youths with hepatic steatosis. The overall goal is to examine whether hepatic DNL is increased in obese youths with steatosis compared to matched controls without steatosis.
Hypotheses: Hepatic conversion of carbohydrates to lipid (DNL) is enhanced and is associated with accumulation of excess liver fat, dyslipidemia and hepatic insulin resistance in obese youths with hepatic steatosis.
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||The Role of Hepatic De Novo Lipogenesis (DNL) in the Pathogenesis of Hepatic Steatosis in Obese Children and Adolescents|
- de novo lipogenesis response to high carbohydrate meal in obese kids with fatty liver [ Time Frame: Study visit 3 ] [ Designated as safety issue: No ]
- de novo lipogenesis response to high carbohydrate meal in obese kids without fatty liver [ Time Frame: Study visit 3 ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||August 2015|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
|Non Fatty liver|
In this study obese youths (12-18 years) will undergo MRI (magnetic resonance imaging) measurement of liver lipid content to determine hepatic fat content. They will undergo a sugary drink (75 grams of glucose and 25 grams of fructose) challenge and Hepatic de novo lipogenesis will be determined as the incorporation of deuterium, from deuterium labeled water (D2O), into plasma triglycerides. Subjects will undergo a 6 hours study assessing de novo lipogenesis, an oral glucose tolerance test, dual energy x-ray absorptiometry, magnetic resonance imaging, and Euglycemic-Hyperinsulinemic Clamp.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01725035
|United States, Connecticut|
|New Haven, Connecticut, United States, 06510|
|Principal Investigator:||Sonia Caprio, M.D.||Yale University|
|Principal Investigator:||Nicola Santoro, M.D./Ph.D,||Yale University|