Harnessing Macrophage Lysosomal Lipid Metabolism in Obesity (ATM)

Bettina Mittendorfer

Status

Enrolling

Conditions

Healthy

Obesity

Diabetes Mellitus, Type 2

Non-Alcoholic Fatty Liver Disease

Study type

Observational

Funder types

Other

NIH

Identifiers

NCT06571474

2098077A

R01DK131188 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Enrollment

60 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

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: