Harnessing Macrophage Lysosomal Lipid Metabolism in Obesity (ATM)

Bettina Mittendorfer

Status: Enrolling

Conditions: Healthy; Nonalcoholic Fatty Liver; Obesity; Diabetes Type 2

Treatments: Other: Dietary consultation weight loss intervention

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06335771

2098077

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 Participants with obesity will complete meetings with study team members for a weight loss intervention to achieve a 10% body weight loss.

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:

• Individuals that do not meet all inclusion Criterion

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

60 participants in 4 patient groups

Lean Individuals

No Intervention group

Description:

No intervention will be administered.

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

Experimental group

Description:

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

Treatment:

Other: Dietary consultation weight loss intervention

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

Experimental group

Description:

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

Treatment:

Other: Dietary consultation weight loss intervention

Individuals with Type 2 Diabetes Mellitus

Experimental group

Description:

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

Treatment:

Other: Dietary consultation weight loss intervention