Harnessing Macrophage Lysosomal Lipid Metabolism in Obesity (ATM)

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