Liver Health and Metabolic Function in People With Obesity

Study Overview
=================
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.

Official Title
-----------------
Liver Health and Metabolic Function in People With Obesity

Conditions
-----------------
Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
-----------------
* Procedure: Weight loss surgery


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Weight loss<br>Participants will undergo weight loss surgery | Procedure: Weight loss surgery<br>* 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.<br>* Other names: Sleeve gastrectomy, Roux-en-Y, biliopancreatic diversion;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatic Fibrogenesis | Rates of liver collagen synthesis | Before and after  20% weightloss, up to 6 months | 
| Liver histology | Analysis of liver tissue morphology | Before and after  20% weightloss, up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | 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 | Before and after  20% weightloss, up to 6 months | 
| Systemic inflammation | Plasma cytokine concentrations | Before and after  20% weightloss, up to 6 months | 
| Tissue bacterial contamination | bacterial 16s ribosomal ribonucleic acid content will be assessed in blood and tissue samples | 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 | 
| Intestinal permeability | Urinary excretion of indigestible sugars will be assessed over 24 hours after an oral challenge | 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 | 
| Liver extracellular vesicles | amount, content and function of extracellular vesicles obtained from liver tissue | at the time of surgery only | 
| 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 |