Liver Health and Metabolic Function in People With Obesity
- Conditions
- Non-Alcoholic Fatty Liver Disease
- Interventions
- Procedure: Weight loss surgery
- Registration Number
- NCT03701828
- Lead Sponsor
- Washington University School of Medicine
- 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.
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 30
- Body mass index ≥35 kg/m2
- Scheduled for Bariatric surgery
- Significant organ disfunction/disease
- Tobacco use
- Previous bariatric surgery
- Pregnancy
- Excessive alcohol use
- Liver disease other than NAFLD
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Weight loss Weight loss surgery Participants will undergo weight loss surgery
- Primary Outcome Measures
Name Time Method Liver histology Before and after ~20% weightloss, up to 6 months Analysis of liver tissue morphology
Hepatic Fibrogenesis Before and after ~20% weightloss, up to 6 months Rates of liver collagen synthesis
- Secondary Outcome Measures
Name Time Method 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
Plasma protein synthesis Before and after ~20% weightloss, up to 6 months Synthesis rates of collagen-related proteins in plasma
Tissue inflammation Before and after ~20% weightloss, up to 6 months adipose tissue and blood immune cell content
Tissue bacterial contamination Before and after ~20% weightloss, up to 6 months bacterial 16s ribosomal ribonucleic acid content will be assessed in blood and tissue samples
Body composition Before and after ~20% weightloss, up to 6 months Body composition assessed by dual-energy x-ray absorptiometry and magnetic resonance scans
Intestinal permeability Before and after ~20% weightloss, up to 6 months Urinary excretion of indigestible sugars will be assessed over 24 hours after an oral challenge
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
Liver extracellular vesicles at the time of surgery only amount, content and function of extracellular vesicles obtained from liver tissue
Systemic inflammation Before and after ~20% weightloss, up to 6 months Plasma cytokine concentrations
Insulin sensitivity Before and after ~20% weightloss, up to 6 months Whole-body insulin sensitivity during a hyperinsulinemic-euglycemic clamp
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
Trial Locations
- Locations (1)
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States