This project aims to determine the effect of significant weight loss on rates on hepatic fibrogenesis in people with obesity.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
23
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.
Washington University School of Medicine
St Louis, Missouri, United States
Liver histology
Analysis of liver tissue morphology
Time frame: Before and after ~20% weightloss, up to 6 months
Hepatic Fibrogenesis
Rates of liver collagen synthesis
Time frame: Before and after ~20% weightloss, up to 6 months
Plasma protein synthesis
Synthesis rates of collagen-related proteins in plasma
Time frame: Before and after ~20% weightloss, up to 6 months
Tissue inflammation
adipose tissue and blood immune cell content
Time frame: Before and after ~20% weightloss, up to 6 months
Systemic inflammation
Plasma cytokine concentrations
Time frame: Before and after ~20% weightloss, up to 6 months
Body composition
Body composition assessed by dual-energy x-ray absorptiometry and magnetic resonance scans
Time frame: Before and after ~20% weightloss, up to 6 months
Adipose histology
Assessment of adipose tissue morphology
Time frame: Before and after ~20% weightloss, up to 6 months
Tissue gene expression
Messenger ribonucleic acid content of adipose, liver and blood tissues will be assessed
Time frame: Before and after ~20% weightloss, up to 6 months
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Tissue lipidomics
bioactive lipid content of adipose, liver and blood tissues will be assessed
Time frame: Before and after ~20% weightloss, up to 6 months
Insulin sensitivity
Whole-body insulin sensitivity during a hyperinsulinemic-euglycemic clamp
Time frame: Before and after ~20% weightloss, up to 6 months
tissue extracellular vesicles
amount, content and function of extracellular vesicles obtained from adipose, liver, and blood tissue
Time frame: Before and after ~20% weightloss, up to 6 months
adipose tissue progenitor cells
content and function of progenitor cells obtained from adipose tissue
Time frame: Before and after ~20% weightloss, up to 6 months
Liver single cell RNA seq
gene expression of liver immune cell types
Time frame: at the time of surgery only
Liver flow cytometry
liver immune cell content
Time frame: at the time of surgery only
Liver lipid turnover
Turnover rates of fatty acids and triglycerides
Time frame: Before and after ~20% weightloss, up to 6 months
PNPLA3 synthesis
Synthesis rate of liver PNPLA3 protein
Time frame: At the time of surgery only