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NCT Number: NCT01725035

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.

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Key information

Conditions

Hepatic Steatosis Digestive System Diseases Fatty Liver Liver Diseases

Age range

12 year–30 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Yale University

New Haven, Connecticut, 06510, United States

About this study

In this study obese youths, adolescents and young adults (12-30 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.

This study record has been re-opened in 2019 and updated to reflect any changes having remained open since its inception with the Yale University IRB and also having obtained additional funding though NIDDK.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Cases will meet the following criteria:
  • BMI higher than 75th percentile
  • Hepatic fat fraction (the amount of fat into the liver) greater or equal than 5.5%
  • Absence of any endocrinopathy
  • Absence of any therapy with medication known to alter glucose metabolism

Controls will meet the following criteria:

  • BMI higher than 75th percentile
  • Hepatic fat fraction (the amount of fat into the liver) lower than 5.5%
  • Absence of any endocrinopathy
  • Absence of any therapy with medication known to alter glucose metabolism
  • Absence of any therapy with medication known to alter glucose metabolism

Exclusion criteria

  • BMI under the 75th percentile
  • Hepatic fat fraction (the amount of fat into the liver) less than 5.5%
  • Absence of any endocrinopathy
  • Any therapy with medication known to alter glucose metabolism

Controls will meet the following criteria:

  • BMI under the 75th percentile
  • Hepatic fat fraction (the amount of fat into the liver) greater than or equal to 5.5%
  • Any endocrinopathy
  • Any therapy with medication known to alter glucose metabolism

Treatment and study plan

Primary outcomes

  1. de novo lipogenesis response to high carbohydrate meal in obese kids with fatty liver

    Time frame: Study visit 3

Secondary outcomes

  1. de novo lipogenesis response to high carbohydrate meal in obese kids without fatty liver

    Time frame: Study visit 3

Sponsors and collaborators

Lead sponsor

Yale University

Other

Collaborators

  • American Heart Association
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Registry information

Official study title

The Role of Hepatic De Novo Lipogenesis (DNL) in the Pathogenesis of Hepatic Steatosis in Obese Children and Adolescents

Acronym: DNL

Important dates

Study start
2010
Primary completion
2022
Study completion
2022
First posted
Nov 12, 2012
Registry last updated
Jun 15, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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