ADRB3 Signaling Pathway in Human Adipose Tissue

Inclusion Criteria:

1. Provision of signed and dated informed consent form 2. Stated willingness tocomply with all study procedures and availability for the duration of the study
2. Males and females 18-70 years old 4. Lean participants, defined as:

• BMI <27 kg/m2

• Normal glucose tolerance defined as fasting glucose less than 100 mg/dL orHbA1c of less than 5.7% at the time of the screening visit 5. Obese Insulinresistant participants, defined as:

• BMI 30-40 kg/m2

• Prediabetes defined as fasting glucose levels of 100 to 125 mg/dL or HbA1c of 5.7% to 6.4%

• Agreement to adhere to Lifestyle Considerations (see section 5.3) throughoutstudy duration

Exclusion Criteria:

1. Diabetes, defined as fasting glucose ≥ 126 mg/dL, HbA1c ≥ 6.5%, or diagnosis ofdiabetes 2. Pregnancy or lactation 3. Currently taking therapeuticanticoagulation which might increase risk of bleeding from fat biopsy (e.g.,warfarin, direct oral anticoagulants) 4. History of eating disorder 5.Currently enrolled in a weight-loss or weight-management program 6. On aspecial or prescribed diet for other reasons (e.g., Celiac disease) 7.Currently taking any medication that is meant for, or has known effect on,appetite 8. Any history of surgical intervention for weight management 9.Abnormal screening labs (renal dysfunction (eGFR < 30 ml/min/1.73 m2), anemia,hypo- or hyperthyroidism, coagulopathy, abnormal liver function (AST, ALT > 3xupper limit of normal) 10. Local or systemic infectious disease with fever orrequiring antibiotic within four weeks of screening visit 11. QTc intervalabove normal or the current use of any concomitant QT-prolonging drug 12. Aclinically significant abnormal ECG 13. Current addiction to alcohol orsubstances of abuse 14. Unwillingness or language barriers precluding adequateunderstanding or cooperation 15. Use of systemic corticosteroids or othermedication known to cause insulin resistance in previous six weeks prior to thescreening visit and throughout the study 16. Diagnosis of bladder outletobstruction or use of antimuscarinic medications for treatment of overactivebladder 17. Use of β-adrenergic receptor blockers or calcium channel blockers
2. Heart disease including Coronary Artery Disease (CAD), Congestive HeartFailure (CHF), or cardiac arrhythmias 19. Uncontrolled sever hypertension (Defined as systolic blood pressure ≥ 180 mm Hg and/or diastolic blood pressure ≥110 mm Hg) 20. Any other condition(s) that might reduce the chance ofobtaining study data, or that might cause safety concerns, or that mightcompromise the ability to give truly informed consent.