Hepatic De Novo Lipogenesis (DNL)in the Pathogenesis of Hepatic Steatosis in Obese Youth
| Status: | Completed |
|---|---|
| Conditions: | Gastrointestinal |
| Therapuetic Areas: | Gastroenterology |
| Healthy: | No |
| Age Range: | 12 - 18 |
| Updated: | 4/21/2016 |
| Start Date: | December 2010 |
| End Date: | April 2016 |
The Role of Hepatic De Novo Lipogenesis (DNL) in the Pathogenesis of Hepatic Steatosis in Obese Children and Adolescents
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.
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.
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.
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.
Inclusion Criteria:
- Cases will meet the following criteria:
- Age between 12 and 18 years
- BMI higher than 85th 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:
- Age between 12 and 18 years
- BMI higher than 85th 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
Exclusion Criteria:
- BMI under the 85th 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 85th 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
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