Bariatric Surgery Candidate, Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, Obesity, Morbid
Conditions
Brief 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.
Detailed 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.
Interventions
None listed
Sponsors
American Society for Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Missouri-Columbia
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
22 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| De novo lipogenesis | Dec 2019 | DNL will be measured directly in the liver biopsies |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Histological scores (NAFLD activity score) | Dec 2019 | 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. |
| Liver enzymes | Dec 2019 | AST and ALT will be measured on the day when liver biopsy is collected |
| FibroScan | Dec 2019 | Liver fat and fibrosis will also be measured non-invasively via FibroScan TM |
Countries
United States
Outcome results
None listed