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

Not Applicable

Active, not recruiting

• Conditions: Metabolic Syndrome; Metabolically Normal Obesity; Non-alcoholic Fatty Liver Disease; Metabolically Abnormal Obesity; Obesity
• Interventions: Other: Weight loss

• Registration Number: NCT01104220
• Lead Sponsor: Washington University School of Medicine

Brief Summary

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.

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 Timeline

• Study Start: 2010-04
• Study First Submitted: 2010-04-13
• Study First Submitted QC: 2010-04-14
• Study First Posted: 2010-04-15
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-15
• Last Update Posted: 2025-04-18
• Primary Completion: 2025-09
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 144

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Obese, scheduled for bariatric surgery	Weight loss	Subjects with a body mass index ≥35.0 kg/m² undergoing bariatric surgery

Primary Outcome Measures

Name	Time	Method
Insulin sensitivity	Baseline	Insulin sensitivity assessed in vivo by using a hyperinsulinemic-euglycemic clamp procedure with stable isotope tracer infusion

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States