Harnessing Macrophage Lysosomal Lipid Metabolism in Obesity

NCT06335771 | Recruiting

• 2 other identifiers: 2098077R01DK131188
• Study Type: interventional
• 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 Participants with obesity will complete meetings with study team members for a weight loss intervention to achieve a 10% body weight loss.

Conditions

Obesity; Nonalcoholic Fatty Liver; Diabetes Type 2; Healthy

Outcome Measures

Primary Outcomes (4)

• Insulin sensitivity assessed as insulin-mediated glucose disposal during a hyperinsulinemic-euglycemic clamp procedure.

  up to 6 months after the intervention

• 24-hour plasma glucose concentration

  up to 6 months after the intervention

• Macrophage isolation in adipose tissue biopsy

  macrophage gene expression using RNA sequencing and fluorescent activated cell sorting (FACS)

  up to 6 months after the intervention

• Macrophage isolation in skeletal muscle tissue

  macrophage gene expression using RNA sequencing and fluorescent activated cell sorting (FACS)

  up to 6 months after the intervention

Study Arms (4)

Lean Individuals

NO INTERVENTION

No intervention will be administered.

Metabolically abnormal obese Individuals (obesity with normoglycemia and abnormal liver fat content)

EXPERIMENTAL

Participants will undergo a dietary weight loss intervention to achieve 10% weight loss over about 6 months.

Other: Dietary consultation weight loss intervention

Metabolically normal obese Individuals (obesity with normoglycemia and normal liver fat content)

EXPERIMENTAL

Participants will undergo a dietary weight loss intervention to achieve 10% weight loss over about 6 months.

Other: Dietary consultation weight loss intervention

Individuals with Type 2 Diabetes Mellitus

EXPERIMENTAL

Participants will undergo a dietary weight loss intervention to achieve 10% weight loss over about 6 months.

Other: Dietary consultation weight loss intervention

Interventions

Dietary consultation weight loss intervention OTHER

Participants will meet with a member of the study team biweekly for about 6 months.

Individuals with Type 2 Diabetes Mellitus; Metabolically abnormal obese Individuals (obesity with normoglycemia and abnormal liver fat content); Metabolically normal obese Individuals (obesity with normoglycemia and normal liver fat content)

Eligibility Criteria

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

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@umsystem.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• 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: March 14, 2024
• First Posted: March 28, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)