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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Weight loss | Experimental | Participants will undergo weight loss surgery |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Weight loss surgery | Procedure | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Liver histology | Analysis of liver tissue morphology | Before and after ~20% weightloss, up to 6 months |
| Hepatic Fibrogenesis | Rates of liver collagen synthesis | Before and after ~20% weightloss, up to 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma protein synthesis | Synthesis rates of collagen-related proteins in plasma | Before and after ~20% weightloss, up to 6 months |
| Tissue inflammation | adipose tissue and blood immune cell content |
| Measure | Description | Time Frame |
|---|---|---|
| PNPLA3 genotype | genotyping for the PNPLA3 SNP rs738409 will be determined | Screening only |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D050110 | Bariatric Surgery |
| D000713 | Anastomosis, Roux-en-Y |
| D015904 | Biliopancreatic Diversion |
| ID | Term |
|---|---|
| D049088 | Bariatrics |
| D000073319 | Obesity Management |
| D013812 | Therapeutics |
| D013514 | Surgical Procedures, Operative |
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|
| Before and after ~20% weightloss, up to 6 months |
| Systemic inflammation | Plasma cytokine concentrations | Before and after ~20% weightloss, up to 6 months |
| Body composition | Body composition assessed by dual-energy x-ray absorptiometry and magnetic resonance scans | Before and after ~20% weightloss, up to 6 months |
| Adipose histology | Assessment of adipose tissue morphology | 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 | Before and after ~20% weightloss, up to 6 months |
| Tissue lipidomics | bioactive lipid content of adipose, liver and blood tissues will be assessed | Before and after ~20% weightloss, up to 6 months |
| Insulin sensitivity | Whole-body insulin sensitivity during a hyperinsulinemic-euglycemic clamp | 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 | Before and after ~20% weightloss, up to 6 months |
| adipose tissue progenitor cells | content and function of progenitor cells obtained from adipose tissue | Before and after ~20% weightloss, up to 6 months |
| Liver single cell RNA seq | gene expression of liver immune cell types | at the time of surgery only |
| Liver flow cytometry | liver immune cell content | at the time of surgery only |
| Liver lipid turnover | Turnover rates of fatty acids and triglycerides | Before and after ~20% weightloss, up to 6 months |
| PNPLA3 synthesis | Synthesis rate of liver PNPLA3 protein | At the time of surgery only |
| D000714 |
| Anastomosis, Surgical |
| D013505 | Digestive System Surgical Procedures |
| D001662 | Biliary Tract Surgical Procedures |