De Novo Lipogenesis in Severity of NAFLD

Bariatric Surgery Candidate Clinical Trial

Official title:

Contribution of de Novo Lipogenesis in Severity of Nonalcoholic Fatty Liver Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03683589
• Other study ID #: 2012544
• Secondary ID: R01DK113701
• Status: Completed
• Start date: February 1, 2019
• Est. completion date: July 31, 2020

Study information

• Verified date: October 2020
• Source: University of Missouri-Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: July 31, 2020
• Est. primary completion date: August 21, 2019
• Gender: All
• Age group: 22 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bariatric Surgery Candidate
• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis
• Obesity, Morbid

Locations

Country	Name	City	State
United States	University of Missouri	Columbia	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
University of Missouri-Columbia	American Society for Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005 May;115(5):1343-51. — View Citation

Lambert JE, Ramos-Roman MA, Browning JD, Parks EJ. Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology. 2014 Mar;146(3):726-35. doi: 10.1053/j.gastro.2013.11.049. Epub 2013 Dec 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	De novo lipogenesis	DNL will be measured directly in the liver biopsies	Dec 2019
Secondary	Histological scores (NAFLD activity score)	Tissue histology will be performed to obtain NAFLD activity score (NAS). A pathologist, trained in determining the NAS of histological samples, grades them for the quantity of fat present, and the levels of inflammation and fibrosis. A score of 0 is considered completely healthy (devoid of any of these three characteristics), while a score of 8 indicates severe pathology, advanced as far as cirrhosis.	Dec 2019
Secondary	Liver enzymes	AST and ALT will be measured on the day when liver biopsy is collected	Dec 2019
Secondary	FibroScan	Liver fat and fibrosis will also be measured non-invasively via FibroScan TM	Dec 2019