Age: 25 - 59
Healthy Volunteers: Not accepted
Inclusion Criteria:
1. Age: 25 - <60 years
2. BMI: 30 - <40 kg/m2 at the first screening visit
3. Within 5% of current weight, for the past 6 months at the first screening visit
4. Able to participate in ergometry testing
5. Has a smart phone, tablet or computer with access to the internet
Exclusion Criteria:
1. If 25-29 years old, > 5% deviation from maximum weight (excluding weights while pregnant) since age 25 years
2. If at least 30 years old, > 5% deviation from maximum weight (excluding weights while pregnant) in last 5 years or ≥ 10% deviation from maximum weight (excluding weights while pregnant) since age 30 years
3. History of pulmonary embolus in the past 6 months
4. Cardiovascular disease (e.g. myocardial infarction, stroke, hospitalization for unstable angina, or transient ischemic attack) within the past 6 months
5. Current major depressive disorder or history of major depressive disorder within 2 years
6. Any regular tobacco or nicotine use in the past year
7. Currently engaging in intense physical training or training for a sports event including, but not limited to, a marathon or body building
8. Currently pregnant, or less than one-year post-partum or actively planning to become pregnant within the next two years
9. Presently classified as being in New York Heart Association Class II or greater or dysrhythmia
10. Diabetes (type 1 or 2 - HbA1c ≥ 6.5%, fasting glucose ≥ 126 mg/dL) or currently taking a glucose lowering medication
11. Thyroid disease requiring hormones or medication or TSH < 0.5 or > 5 mIU/L
12. Renal disease requiring dialysis
13. Known HIV infection
14. ALT or AST greater than 5 times the upper limit of normal or active gall bladder disease
15. Significant anemia (Hgb < 10 g/dL) or thrombocytopenia (platelet count < 60,000 /mm3)
16. Leukopenia defined as:
Males: WBC < 3,100 /mm3 or (WBC 3,100 - < 4,000 /mm3 and at least 1 Duffy antigen (A, B) positive or no result) Females: WBC < 3,400 /mm3 or (WBC 3,400 - < 4,000 /mm3 and at least 1 Duffy antigen (A, B) positive or no result)
17. Active cancer or current chemotherapy treatment, or history of cancer requiring treatment in the past 5 years except for non-melanoma skin cancers or cancers that have clearly been cured
18. Current or past history of anorexia nervosa or bulimia nervosa
19. Current or past diagnosis of binge eating disorder
20. Diagnosis of other severe psychiatric disorder (e.g. schizophrenia, bipolar disorder)
21. Unwillingness to abstain from marijuana/cannabis use for 3 weeks at each of the four assessment time points
22. Known or suspected abuse or misuse of alcohol, prescription drugs, or recreational drugs
23. Antiretroviral therapy (ART), including treatment for HIV, pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) within the past 3 months
24. Regularly taking medication or supplement known to affect appetite, energy expenditure, or weight (e.g. appetite suppressants, steroids-including inhaled steroids but not topical, alpha-blockers, beta-blockers, certain psychotropic medications)
25. Currently taking anticoagulant medication
26. Currently enrolled in a supervised weight reduction program
27. Prior or planned bariatric surgery, endoscopic therapy, device-based therapy for obesity, liposuction, cryolipolysis, or abdominoplasty
28. Severely restricted diets: Vegan (no meat, fish, dairy, eggs, or honey), very low carbohydrate (<15% calorie as carbohydrate), very low fat (<15% calories as fat), or strictly gluten free
29. Current celiac or diagnosed gluten intolerance or inflammatory bowel disease requiring specialized diet
30. Night or rotating shift worker
31. Known severe allergy (e.g. anaphylaxis) to nuts or other foods
32. Systolic blood pressure (BP) <90 mmHg and/or diastolic BP <60 mmHg on 2 measurements during the clinical screening visit.
33. Systolic blood pressure (BP) >160 mmHg and/or diastolic BP >100 mmHg on at least 2 measurements during the clinical screening visit or resting heart rate < 45 beats per minute or >100 on 2 measurements during the clinical screening visit.
34. Metal implants, piercings that cannot be removed, or metal-based tattoos or hair treatments
35. Exceeds limitations to fit dual-energy X-ray absorptiometry (DXA) field of view
36. Known allergy to lidocaine or acetaminophen
37. Non-compliance with appointments or tasks (food diaries, etc.) during the screening phase
38. Blood clotting disorder or INR > ULN or PT > ULN or (a)PTT > ULN
39. Tendency to form thick or raised scars
40. Inability to achieve weight stability (defined in section 4.2.1) during the 2 weeks prior to initiation of the baseline Doubly Labeled Water (DLW) assessment
41. At high risk for suicide, as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)