Liver Health and Metabolic Function in People With Obesity

This project aims to determine the effect of significant weight loss on rates on hepatic fibrogenesis in people with obesity.

Study Overview

• Status: Completed
• Conditions: Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Procedure: Weight loss surgery

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Weight loss; Participants will undergo weight loss surgery	Procedure: Weight 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.; 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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PNPLA3 genotype	genotyping for the PNPLA3 SNP rs738409 will be determined	Screening only

Collaborators and Investigators

• Sponsor: Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Actual): February 19, 2024
• Study Completion (Actual): February 19, 2024

Study Registration Dates

• First Submitted: September 10, 2018
• First Submitted That Met QC Criteria: October 8, 2018
• First Posted (Actual): October 10, 2018

Study Record Updates

• Last Update Posted (Actual): June 19, 2025
• Last Update Submitted That Met QC Criteria: June 17, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 201808128

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No