Harnessing Macrophage Lysosomal Lipid Metabolism in Obesity (ATM) (ATM)

Harnessing Macrophage Lysosomal Lipid Metabolism in Obesity-Associated Diseases

The goal of this study is to evaluate the role of transcription factor EB (TFEB) in adipose (fat) tissue macrophages (ATM) in regulating adipose tissue and systemic metabolic function in obesity. The investigators will assess the differences in ATM lipid metabolism in people with metabolically abnormal obesity and lean individuals.

Both groups will have:

• screening visit
• imaging (body composition testing - dual-energy x-ray absorptiometry (DEXA) scans, magnetic resonance imaging [MRI] and magnetic resonance spectroscopy [MRS] scans)
• Overnight visit with intravenous infusion (IV), muscle, and fat tissue biopsies

Study Overview

• Status: Recruiting
• Conditions: Healthy; Obesity; Diabetes Mellitus, Type 2; Non-Alcoholic Fatty Liver Disease

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Heather McHatton; Phone Number: 573-882-7619; Email: heathermchatton@health.missouri.edu
• Study Contact Backup: Name: Aman Pritish Aher; Email: amanpritishaher@missouri.edu

Study Locations

• United States
  • Missouri
    • Columbia, Missouri, United States, 65212
      • Recruiting
      • University of Missouri School of Medicine
      • Contact: Bettina Mittendorfer; Phone Number: 573-882-9377; Email: b.mittendorfer@missouri.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

All Volunteers , separated into 4 groups as per eligibility Criterion.

Description

Inclusion Criteria :

• age: ≥18 but ≤70 years
• not pregnant or breastfeeding
• weight stable and sedentary before enrollment
• no use tobacco products, excessive amounts of alcohol, or dietary supplements, or medications known to or suspected to affect glucose and lipid metabolism (aside from certain medications used to treat diabetes in the metabolically abnormal obesity [MAO]-Type 2 Diabetes group)
• no evidence of significant organ system dysfunction or disease (e.g. chronic severe kidney disease, cancer)
• participants must fulfil all of the following group-specific inclusion criteria below:

Lean group:

• Body mass index (BMI) ≥18.5 but <25.0 kg/m2
• Intrahepatic triglyceride (IHTG) content <5%
• fasting blood glucose concentration: <100 mg/dl
• blood glucose concentration 2 h after a 75 g oral glucose challenge: <140 mg/dl
• Hemoglobin A1C (HbA1c) <5.7 %

Metabolically normal obesity (MNO) group:

• BMI ≥30.0 but <45.0 kg/m2
• IHTG content <5%
• fasting blood glucose concentration: <100 mg/dl
• blood glucose concentration 2 h after a 75 g oral glucose challenge: <140 mg/dl
• HbA1c <5.7 %

Metabolically abnormal obesity (MAO)-insulin resistance and non-alcoholic fatty liver disease (NAFLD) group:

• BMI ≥30.0 but <45.0 kg/m2
• IHTG content >7.5%
• fasting blood glucose concentration: ≥100 but <126 mg/dl
• blood glucose concentration 2 h after a 75 g oral glucose challenge: ≥140 but <200 mg/dl
• HbA1c: ≥5.7 but <6.4 %

MAO-type 2 diabetes group:

• BMI ≥30.0 but <45.0 kg/m2
• clinical diagnosis of type 2 diabetes or fasting blood glucose concentration >126 mg/dl or blood glucose concentration 2 h after a 75 g oral glucose challenge>200 mg/dl or HbA1c >6.4 % without medication if not diagnosed and medically treated for diabetes

Exclusion Criteria:

- Individuals that do not meet all inclusion Criterion

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Lean Individuals; No intervention will be administered.
Metabolically abnormal obese Individuals; Obesity with normoglycemia and abnormal liver fat content
Metabolically normal obese Individuals; Obesity with normoglycemia and normal liver fat content
Individuals with Type 2 Diabetes Mellitus; Pre-Diagnosed type 2 diabetics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin sensitivity	Sensitivity assessed as insulin-mediated glucose disposal during a hyperinsulinemic-euglycemic clamp procedure	Within 2 weeks of Clinical Visit
24-hour plasma glucose concentration		Within 2 weeks of Clinical Visit
Macrophage isolation in adipose tissue biopsy	macrophage gene expression using RNA sequencing and fluorescent activated cell sorting (FACS)	Within 2 weeks of Clinical Visit
Macrophage isolation in skeletal muscle tissue	macrophage gene expression using RNA sequencing and fluorescent activated cell sorting (FACS)	Within 2 weeks of Clinical Visit

Collaborators and Investigators

• Sponsor: Bettina Mittendorfer
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Washington University School of Medicine; National Institutes of Health (NIH)
• Investigators: Principal Investigator: Bettina Mittendorfer, University of Missouri-Columbia

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: August 22, 2024
• First Submitted That Met QC Criteria: August 22, 2024
• First Posted (Actual): August 26, 2024

Study Record Updates

• Last Update Posted (Actual): July 22, 2025
• Last Update Submitted That Met QC Criteria: July 16, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Digestive System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Overweight; Obesity; Diabetes Mellitus, Type 2; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 2098077A; R01DK131188 (U.S. NIH Grant/Contract)

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
• product manufactured in and exported from the U.S.: No