A Study to Investigate Why Overweight People Regain Weight After Losing Weight in a Behavioral Weight Loss Program

Inclusion Criteria:

1. Age: 25 - <60 years

2. BMI: 30 - <40 kg/m2

3. Within 5% of current weight, for the past 6 months

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 whilepregnant) since age 25 years

2. If at least 30 years old, > 5% deviation from maximum weight (excluding weightswhile pregnant) in last 5 years or ≥ 10% deviation from maximum weight (excludingweights 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 forunstable angina, or transient ischemic attack) within the past 6 months

5. Current major depressive disorder or history of major depressive disorder within 2years

6. Any regular tobacco or nicotine use in the past year

7. Currently engaging in intense physical training or training for a sports eventincluding, but not limited to, a marathon or body building

8. Currently pregnant, or less than one-year post-partum or actively planning to becomepregnant within the next two years

9. Presently classified as being in New York Heart Association Class II or greater ordysrhythmia

10. Diabetes (type 1 or 2 - HbA1c ≥ 6.5%, fasting glucose ≥ 126 mg/dL) or currentlytaking 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 bladderdisease

15. Significant anemia (Hgb < 10 g/dL), leukopenia (WBC < 4,000 /mm3), orthrombocytopenia (platelet count < 60,000 /mm3)

16. Active cancer or current chemotherapy treatment, or history of cancer requiringtreatment in the past 5 years except for non-melanoma skin cancers or cancers thathave clearly been cured

17. Current or past history of anorexia nervosa or bulimia nervosa

18. Current or past diagnosis of binge eating disorder

19. Diagnosis of other severe psychiatric disorder (e.g. schizophrenia, bipolardisorder)

20. Unwillingness to abstain from marijuana/cannabis use for 3 weeks at each of the fourassessment time points

21. Known or suspected abuse or misuse of alcohol, prescription drugs, or recreationaldrugs

22. Antiretroviral therapy (ART), including treatment for HIV, pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) within the past 3 months

23. Regularly taking medication or supplement known to affect appetite, energyexpenditure, or weight (e.g. appetite suppressants, steroids-including inhaledsteroids but not topical, alpha-blockers, beta-blockers, certain psychotropicmedications)

24. Currently taking anticoagulant medication

25. Currently enrolled in a supervised weight reduction program

26. Prior or planned bariatric surgery, endoscopic therapy, device-based therapy forobesity, liposuction, cryolipolysis, or abdominoplasty

27. Severely restricted diets: Vegan (no meat, fish, dairy, eggs, or honey), very lowcarbohydrate (<15% calorie as carbohydrate), very low fat (<15% calories as fat), orstrictly gluten free

28. Current celiac or diagnosed gluten intolerance or inflammatory bowel diseaserequiring specialized diet

29. Night or rotating shift worker

30. Known severe allergy (e.g. anaphylaxis) to nuts or other foods

31. Systolic blood pressure (BP) <90 mmHg and/or diastolic BP <60 mmHg on 2 measurementsduring the clinical screening visit.

32. Systolic blood pressure (BP) >160 mmHg and/or diastolic BP >100 mmHg on at least 2measurements during the clinical screening visit or resting heart rate < 45 beatsper minute or >100 on 2 measurements during the clinical screening visit.

33. Metal implants, piercings that cannot be removed, or metal-based tattoos or hairtreatments

34. Exceeds limitations to fit MRI and dual-energy X-ray absorptiometry (DXA) field ofview

35. Known allergy to lidocaine or acetaminophen

36. Non-compliance with appointments or tasks (food diaries, etc.) during the screeningphase

37. Blood clotting disorder or INR > ULN or PT > ULN or (a)PTT > ULN

38. Tendency to form thick or raised scars

39. Inability to achieve weight stability (defined in section 4.2.1) during the 2 weeksprior to initiation of the baseline Doubly Labeled Water (DLW) assessment

40. At high risk for suicide, as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)