Harnessing Macrophage Lysosomal Lipid Metabolism in Obesity (ATM)

NCT06571474 | Recruiting

• 2 other identifiers: 2098077AR01DK131188
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Obesity; Non-Alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Healthy

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (4)

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

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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)
• 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

Sponsors & Collaborators

• Bettina Mittendorfer: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Washington University School of Medicine: collaborator

Study Sites (1)

University of Missouri School of Medicine

Columbia, Missouri, 65212, United States

RECRUITING

MeSH Terms

Conditions

Obesity; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Fatty Liver; Liver Diseases; Digestive System Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Study Officials

• Bettina Mittendorfer

  University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heather McHatton

CONTACT

573-882-7619; heathermchatton@health.missouri.edu

Aman Pritish Aher

CONTACT

amanpritishaher@missouri.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior Associate Dean for Research; Professor, Medicine & Nutrition; NextGen Director of Clinical and Translational Sciences Unit

Study Record Dates

• First Submitted: August 22, 2024
• First Posted: August 26, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: July 22, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)