De Novo Lipogenesis in Severity of NAFLD
| Status: | Recruiting |
|---|---|
| Conditions: | Obesity Weight Loss, Gastrointestinal, Gastrointestinal, Hepatitis |
| Therapuetic Areas: | Endocrinology, Gastroenterology, Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 22 - 65 |
| Updated: | 3/15/2019 |
| Start Date: | February 1, 2019 |
| End Date: | December 31, 2019 |
| Contact: | Majid Mufaqam Syed Abdul, MS |
| Email: | ms9rf@mail.missouri.edu |
| Phone: | 5738842014 |
Contribution of de Novo Lipogenesis in Severity of Nonalcoholic Fatty Liver Disease
NAFLD is the most prevalent liver disease in the U.S., and there is a serious need to
understand its progression to the advanced state, nonalcoholic steatohepatitis (NASH).
Previous studies has shown that elevated de novo lipogenesis (DNL) is the unique, early event
distinguishing patients with NAFLD from equally-obese subjects with low IHTG. The purpose of
this study is to directly by measure DNL in human liver tissue and comparing it to liver
histological scores from patient biopsies.
understand its progression to the advanced state, nonalcoholic steatohepatitis (NASH).
Previous studies has shown that elevated de novo lipogenesis (DNL) is the unique, early event
distinguishing patients with NAFLD from equally-obese subjects with low IHTG. The purpose of
this study is to directly by measure DNL in human liver tissue and comparing it to liver
histological scores from patient biopsies.
The development of nonalcoholic fatty liver disease (NAFLD) progresses from a state of
elevated intrahepatic triglycerides (IHTG) to liver inflammation, and ultimately, hepatic
apoptosis and fibrosis. NAFLD is the most prevalent liver disease in the U.S., and there is a
serious need to understand its progression to the advanced state, nonalcoholic
steatohepatitis (NASH). Elevated de novo lipogenesis (DNL) is the unique, early event
distinguishing patients with NAFLD from equally-obese participants with low IHTG. DNL is the
process of liver synthesis of fatty acids (FAs) from carbohydrate. In humans, studies have
shown that DNL significantly predicts the magnitude of IHTG, however, it is unknown whether
the pathway plays a role in disease progression. Evidence supporting this concept includes
the fact that the primary product of DNL is the saturated FA, palmitate, which in cell
culture has been shown to significantly contribute to oxidative stress and inflammation.
Recent rodent data show that upregulation of DNL through dietary supplementation of sucrose
exacerbated the hepatotoxic effects of excess dietary FAs. A preliminary abstract presented
by others at the 2017 Liver Meeting suggested that DNL may not be different between patients
with low and high liver fibrosis, although these data were collected using an indirect
measure of liver disease. Here, in the present study, the hypothesis will be tested directly
by measuring DNL in human liver tissue and comparing it to liver histological scores (NAFLD
Activity Score, NAS) from patient samples.
elevated intrahepatic triglycerides (IHTG) to liver inflammation, and ultimately, hepatic
apoptosis and fibrosis. NAFLD is the most prevalent liver disease in the U.S., and there is a
serious need to understand its progression to the advanced state, nonalcoholic
steatohepatitis (NASH). Elevated de novo lipogenesis (DNL) is the unique, early event
distinguishing patients with NAFLD from equally-obese participants with low IHTG. DNL is the
process of liver synthesis of fatty acids (FAs) from carbohydrate. In humans, studies have
shown that DNL significantly predicts the magnitude of IHTG, however, it is unknown whether
the pathway plays a role in disease progression. Evidence supporting this concept includes
the fact that the primary product of DNL is the saturated FA, palmitate, which in cell
culture has been shown to significantly contribute to oxidative stress and inflammation.
Recent rodent data show that upregulation of DNL through dietary supplementation of sucrose
exacerbated the hepatotoxic effects of excess dietary FAs. A preliminary abstract presented
by others at the 2017 Liver Meeting suggested that DNL may not be different between patients
with low and high liver fibrosis, although these data were collected using an indirect
measure of liver disease. Here, in the present study, the hypothesis will be tested directly
by measuring DNL in human liver tissue and comparing it to liver histological scores (NAFLD
Activity Score, NAS) from patient samples.
Inclusion and exclusion criteria are similar to the criteria set by a larger project
(NCT03151798).
Inclusion criteria:
- Men and women (pre and post-menopausal)
- Overweight/obese with BMI ≥ 25.9 or ≤ 50.0 kg/m2
- Characteristics of the metabolic syndrome, pre-diabetes (fasting glucose 100-125 mg/dL
or 2h glucose 140-200 mg/dL) or diabetes type II
- 22-65 years of age
- use of tobacco products or no use of these products
- Sedentary, ≤ 60 minutes per week of structured physical activity
Exclusion criteria:
• The following conditions exclude subjects for this project because bariatric surgery
would not be performed in these populations. Individuals with acute disease or advanced
cardiac, liver, or renal disease, excessive alcohol use, anticoagulation therapy, or any
severe co-morbid condition limiting life expectancy < 1 year. Women pregnant or trying to
become pregnant.
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