Non-Alcoholic Fatty Liver Disease
Conditions
Brief summary
This project aims to determine the effect of significant weight loss on rates on hepatic fibrogenesis in people with obesity.
Detailed description
Non-alcoholic fatty liver disease (NAFLD) affects approximately 70% of those with obesity and if left untreated can progress to cirrhosis and liver failure. NAFLD stages progress from the stage of simple steatosis to steatohepatitis, and fibrosis The stage of NAFLD is currently best determined using histology from a liver biopsy, however this provides a static depiction of the state of the liver. Therefore, this project aims to determine fibrogenesis in the liver of obese humans in vivo, before and after weight loss.
Interventions
PROCEDUREWeight loss surgery
All surgery types will be included. However, only participants scheduled for surgery with collaborating surgeons will be included. Surgery is not provided by study team.
Sponsors
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index ≥35 kg/m2 * Scheduled for Bariatric surgery
Exclusion criteria
* Significant organ disfunction/disease * Tobacco use * Previous bariatric surgery * Pregnancy * Excessive alcohol use * Liver disease other than NAFLD
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic Fibrogenesis | Before and after ~20% weightloss, up to 6 months | Rates of liver collagen synthesis |
| Liver histology | Before and after ~20% weightloss, up to 6 months | Analysis of liver tissue morphology |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tissue inflammation | Before and after ~20% weightloss, up to 6 months | adipose tissue and blood immune cell content |
| Systemic inflammation | Before and after ~20% weightloss, up to 6 months | Plasma cytokine concentrations |
| Body composition | Before and after ~20% weightloss, up to 6 months | Body composition assessed by dual-energy x-ray absorptiometry and magnetic resonance scans |
| Adipose histology | Before and after ~20% weightloss, up to 6 months | Assessment of adipose tissue morphology |
| Tissue gene expression | Before and after ~20% weightloss, up to 6 months | Messenger ribonucleic acid content of adipose, liver and blood tissues will be assessed |
| Tissue lipidomics | Before and after ~20% weightloss, up to 6 months | bioactive lipid content of adipose, liver and blood tissues will be assessed |
| tissue extracellular vesicles | Before and after ~20% weightloss, up to 6 months | amount, content and function of extracellular vesicles obtained from adipose, liver, and blood tissue |
| adipose tissue progenitor cells | Before and after ~20% weightloss, up to 6 months | content and function of progenitor cells obtained from adipose tissue |
| Liver single cell RNA seq | at the time of surgery only | gene expression of liver immune cell types |
| Liver flow cytometry | at the time of surgery only | liver immune cell content |
| Liver lipid turnover | Before and after ~20% weightloss, up to 6 months | Turnover rates of fatty acids and triglycerides |
| PNPLA3 synthesis | At the time of surgery only | Synthesis rate of liver PNPLA3 protein |
| Insulin sensitivity | Before and after ~20% weightloss, up to 6 months | Whole-body insulin sensitivity during a hyperinsulinemic-euglycemic clamp |
| Plasma protein synthesis | Before and after ~20% weightloss, up to 6 months | Synthesis rates of collagen-related proteins in plasma |
Other
| Measure | Time frame | Description |
|---|---|---|
| PNPLA3 genotype | Screening only | genotyping for the PNPLA3 SNP rs738409 will be determined |
Countries
United States
Outcome results
None listed