Adaptive Immune Response in Visceral and Subcutaneous Fat: Role in Human Insulin Resistance

The proposed study is designed to test the hypothesis that in human obesity, the balance of pro- and anti-inflammatory T cells in fat tissue is in fact related to macrophage phenotype and insulin resistance, and how it is related.

This study is needed to confirm whether conclusions based on studies of visceral adipose tissue in mice are indeed applicable to humans.

We also want to determine the relationship between insulin resistance/hyperinsulinemia and ability to lose weight in obese individuals.

Study Overview

• Status: Enrolling by invitation
• Conditions: Inflammation; Obesity; Insulin Resistance; Insulin Sensitivity

Detailed Description

Previous studies have found convincing evidence of the relationship between insulin resistance, T cell profiles, macrophage profiles and inflammation of the fat cells. This study will add human subjects to that body of evidence.

Overview Aim 1: Test the hypothesis that the balance of anti- inflammatory vs proinflammatory T cells is protective for systemic insulin resistance. T cell profiles in subcutaneous and visceral tissue and blood will be compared in IR vs IS obese humans at baseline and potentially after 12 months following weight loss. Tcell profile will be evaluated for relationships with IR and inflammation, with adjustment for total body fat. Secondarily, they will be evaluated for relationship to adipose cell size.

Overview Aim 2: Test the hypothesis that macrophage phenotype in adipose tissue is associated with T cell profile and IR. Frequency of macrophage phenotypes (M1 vs M2) will be analyzed in IR vs IS obese humans at baseline and potentially after 12 months following weight loss.

Overview Aim 3: Testing the hypothesis insulin resistance is associated with T cell receptor phenotypes in subcutaneous and visceral tissue. IR and IS subjects will be evaluated at baseline by sequencing of expressed TCRs in paired SAT, VAT, and blood. We will determine whether TCR phenotypes are shared between different IR individuals.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

There are no restrictions in regards to gender, race, or socioeconomic status. The racial/ ethnic composition of the study population will be reflective of the communities surrounding the Stanford University Medical Center.

Description

Inclusion Criteria:

• Current patients of Stanford Healthcare, Bariatric Surgery Clinic, scheduled to undergo bariatric surgery (sleeve or RYGB)
• BMI 30-55kg/m2
• 30-65 years of age
• good general health, no major organ disease
• non-diabetic by current American Diabetes Association (ADA) criteria (fasting glucose <126mg/dl)

Exclusion Criteria:

• Subjects with any clinical or biochemical evidence of significant anemia, gastrointestinal, cardiac, hepatic or renal disease will be excluded.
• Subjects with other medical problems may participate as long as the problems are stable.
• Subjects with active psychiatric disorders or past history of bariatric surgery
• Pregnant or lactating women will also be excluded from the study, due to possible risk to the fetus or infant.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Bariatric Cohort; For consenting subjects who are undergoing bariatric surgery, a visceral fat sample will be taken during surgery. In addition to the fat sample, insulin resistance will be measured and determined by a modification of the insulin suppression test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T-cell profile in visceral and subcutaneous fat	Pro-inflammatory and anti-inflammatory T cell profiles in subcutaneous adipose tissue and visceral adipose tissue measured via flow cytometry.	baseline (within 2 months prior to bariatric surgery)
T-cell profile in visceral and subcutaneous fat	Pro-inflammatory and anti-inflammatory T cell profiles in subcutaneous adipose tissue and visceral adipose tissue measured via flow cytometry.	post-operatively (1-2 years status post bariatric surgery)
Adipose cell size associated with T cell profile and IR.	Cell size of subcutaneous adipose tissue and visceral adipose tissue measured via flow cytometry.	baseline (within 2 months prior to bariatric surgery)
Adipose cell size associated with T cell profile and IR.	Cell size of subcutaneous adipose tissue and visceral adipose tissue measured via flow cytometry.	post-operatively (1-2 years status post bariatric surgery)
Macrophage phenotype	Frequency of macrophage phenotype (M1 vs M2) in subcutaneous adipose tissue and visceral adipose tissue measured via flow cytometry.	(Timeframe: baseline (within 2 months prior to bariatric surgery)
Macrophage phenotype	Frequency of macrophage phenotype (M1 vs M2) in subcutaneous adipose tissue and visceral adipose tissue measured via flow cytometry.	post-operatively (1-2 years status post bariatric surgery)
T cell receptor phenotypes	Frequency of T-cell receptors in subcutaneous adipose tissue and visceral adipose tissue measured via flow cytometry.	(Timeframe: baseline (within 2 months prior to bariatric surgery)
T cell receptor phenotypes	Frequency of T-cell receptors in subcutaneous adipose tissue and visceral adipose tissue measured via flow cytometry.	post-operatively (1-2 years status post bariatric surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in body weight	Percent body weight loss post bariatric surgery, accounting for insulin sensitivity, T-cell profile, cell size, and macrophage and T-cell phenotypes.	(Timeframe: baseline (within 2 months prior to bariatric surgery)
Change in body weight	Percent body weight loss post bariatric surgery, accounting for insulin sensitivity, T-cell profile, cell size, and macrophage and T-cell phenotypes.	post-operatively (1-2 years status post bariatric surgery)

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Tracey McLaughlin, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: July 3, 2018
• First Submitted That Met QC Criteria: January 11, 2021
• First Posted (Actual): January 14, 2021

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Hyperinsulinism; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Inflammation; Insulin Resistance
• Other Study ID Numbers: 40196; 1-19-ICTS-073 (Other Grant/Funding Number: American Diabetes Association)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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