De Novo Lipogenesis in Severity of NAFLD

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

49 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-02-01

Study Completion Date

2020-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Nonalcoholic Fatty Liver Disease Nonalcoholic Steatohepatitis Bariatric Surgery Candidate Obesity, Morbid

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Study group

Participants will receive deuterated water for 10 days before undergoing bariatric surgery.

Liver biopsy collected, lipids extracted and DNL measured via GC/MS.

No interventions assigned to this group

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

Minimum Eligible Age

22 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Elizabeth Jane Parks

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Elizabeth J Parks, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Missouri-Columbia

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Missouri

Columbia, Missouri, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND

PMID: 24316260 (View on PubMed)

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. doi: 10.1172/JCI23621.

Reference Type BACKGROUND

PMID: 15864352 (View on PubMed)

Syed-Abdul MM, Moore MP, Wheeler AA, Ganga RR, Diaz-Arias A, Petroski GF, Rector RS, Ibdah JA, Parks EJ. Isotope Labeling and Biochemical Assessment of Liver-Triacylglycerol in Patients with Different Levels of Histologically-Graded Liver Disease. J Nutr. 2023 Dec;153(12):3418-3429. doi: 10.1016/j.tjnut.2023.09.018. Epub 2023 Sep 27.

Reference Type DERIVED

PMID: 37774841 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

R01DK113701

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2012544

Identifier Type: -

Identifier Source: org_study_id