Role of Immune System in Obesity-related Inflammation and Cardiometabolic Risk

The purpose of this study is to learn more about how the body stores fat in and around organs (for example in the liver) and why this affects some people's health more than others. Understanding this may lead to better treatments for diseases such as diabetes and cardiovascular disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Metabolically Abnormal Obesity; Metabolically Normal Obesity
• Intervention / Treatment: Other: Weight loss

Detailed Description

The purpose of this study is to determine the specific cellular and organ system metabolic and immunologic alterations that are associated with insulin resistance and inflammation in order to identify putative mechanisms and novel bio-markers involved in the pathogenesis and progression of inflammatory and cardiometabolic diseases.

• Study Type: Interventional
• Enrollment (Estimated): 144
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Lean, metabolically healthy group - Body mass index (BMI) 18.5-24.9 kg/m2, HbA1C ≤5.6%, fasting plasma glucose concentration <100 mg/dl, 2-h OGTT plasma glucose concentration <140 mg/dl and intrahepatic triglyceride (IHTG) content ≤5%.

Obese, metabolically healthy group - BMI ≥30 kg/m2, HHbA1C ≤5.6%, fasting plasma glucose concentration <100 mg/dl, 2-h OGTT plasma glucose concentration <140 mg/dl and intrahepatic triglyceride (IHTG) content ≤5%.

Obese, metabolically healthy group - BMI ≥30 kg/m2, IHTG content ≥5.6% and HbA1C ≥5.7% or fasting plasma glucose concentration ≥100 mg/dl or 2-h OGTT plasma glucose concentration ≥140 mg/dl.

Lean, scheduled for inguinal hernia, hysterectomy or myomectomy surgery - BMI 18.5-24.9 kg/m2, HbA1C ≤5.6%, fasting plasma glucose concentration <100 mg/dl, 2-h OGTT plasma glucose concentration <140 mg/dl and IHTG content ≤5%.

Obese, scheduled for bariatric and gallbladder surgery - BMI ≥35.0kg/m2

Exclusion Criteria:

• active or previous history of liver diseases other than NAFLD
• history of alcohol abuse
• currently consuming ≥20 g alcohol/day
• severe hypertriglyceridemia (>300 mg/dL)
• smoke tobacco
• cancer diagnosis within the previous 5 years
• medications that might confound the study results
• pregnancy or lactation
• exercise >2 h/week

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Lean, metabolically normal; Subjects with body mass index 18.5 - 24.9 kg/m² and normal fasting blood glucose and oral glucose tolerance and liver fat.
No Intervention: Obese, metabolically normal; Subjects with body mass index ≥30.0 kg/m² and normal fasting blood glucose and oral glucose tolerance and liver fat.
No Intervention: Obese, metabolically abnormal; Subjects with body mass index ≥30.0 kg/m² and impaired fasting or oral glucose tolerance and increased liver fat.
Experimental: Obese, scheduled for bariatric surgery; Subjects with a body mass index ≥35.0 kg/m² undergoing bariatric surgery	Other: Weight loss; Bariatric surgery-induced weight loss to achieve ~20%-30% reduction in initial body weight
No Intervention: Obese, scheduled for gallbladder surgery; Subjects with a body mass index ≥35.0 kg/m² undergoing gallbladder surgery
No Intervention: Lean, scheduled for inguinal hernia, hysterectomy or myomectomy surgery; Subjects with body mass index 18.5 - 24.9 kg/m² and normal fasting blood glucose and oral glucose tolerance and liver fat.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin sensitivity	Insulin sensitivity assessed in vivo by using a hyperinsulinemic-euglycemic clamp procedure with stable isotope tracer infusion	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TNF-alpha	TNF-alpha is a marker of inflammation	Baseline
Interleukin-6 (IL-6)	Interleukin-6 is a marker of inflammation	Baseline
Liver tissue inflammation	Liver immune cell content	Baseline
Abdominal adipose tissue inflammation	Subcutaneous, omental and transverse mesocolic adipose tissue	Baseline only in participants scheduled for bariatric surgery
Abdominal adipose tissue inflammation	Subcutaneous and omental adipose tissue	Baseline only in participants scheduled for gallbladder, inguinal hernia, hysterectomy or myomectomy surgery
Upper vs lower adipose tissue inflammation	Immune cell content in abdominal and femoral subcutaneous adipose tissue	Baseline (All groups)
Exosome-mediated intercellular signaling	Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood, subcutaneous, omental and transverse mesocolic adipose tissue and liver.	Baseline only in participants scheduled for bariatric surgery
Exosome-mediated intercellular signaling	Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood, subcutaneous and omental adipose tissue	Baseline only in participants scheduled for gallbladder, inguinal hernia, hysterectomy or myomectomy surgery
Exosome-mediated intercellular signaling	Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood and abdominal and femoral subcutaneous adipose tissue.	Baseline only in all participants
Change in exosome-mediated intercellular signaling	Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood and adipose tissue	Before and after 20-30% weight loss (~3-4 months) in participants scheduled for bariatric surgery
Hepatic PNPLA3 synthesis rate	Synthesis rates assessed by stable isotope techniques in the fasted vs the fed states	Baseline only in people scheduled for gallbladder or bariatric surgery

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Pfizer
• Investigators: Principal Investigator: Samuel Klein, M.D., Washington University School of Medicine

Publications and helpful links

General Publications

• Yoshino J, Patterson BW, Klein S. Adipose Tissue CTGF Expression is Associated with Adiposity and Insulin Resistance in Humans. Obesity (Silver Spring). 2019 Jun;27(6):957-962. doi: 10.1002/oby.22463. Epub 2019 Apr 19.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2010
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 13, 2010
• First Submitted That Met QC Criteria: April 14, 2010
• First Posted (Estimated): April 15, 2010

Study Record Updates

• Last Update Posted (Estimated): October 23, 2025
• Last Update Submitted That Met QC Criteria: October 22, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Obesity; Metabolic syndrome; NAFLD
• Additional Relevant MeSH Terms: Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Digestive System Diseases; Glucose Metabolism Disorders; Liver Diseases; Insulin Resistance; Hyperinsulinism; Overweight; Fatty Liver; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 201102127

Drug and device information, study documents

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