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

Eligibility 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
• 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), leukopenia (WBC \< 4,000 /mm3), or thrombocytopenia (platelet count \< 60,000 /mm3)
• 16. 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
• 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, bipolar disorder)
• 20. Unwillingness to abstain from marijuana/cannabis use for 3 weeks at each of the four assessment time points
• 21. Known or suspected abuse or misuse of alcohol, prescription drugs, or recreational drugs
• 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, energy expenditure, or weight (e.g. appetite suppressants, steroids-including inhaled steroids but not topical, alpha-blockers, beta-blockers, certain psychotropic medications)
• 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 for obesity, liposuction, cryolipolysis, or abdominoplasty
• 27. 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
• 28. Current celiac or diagnosed gluten intolerance or inflammatory bowel disease requiring 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 measurements during the clinical screening visit.
• 32. 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.
• 33. Metal implants, piercings that cannot be removed, or metal-based tattoos or hair treatments
• 34. Exceeds limitations to fit MRI and dual-energy X-ray absorptiometry (DXA) field of view
• 35. Known allergy to lidocaine or acetaminophen
• 36. Non-compliance with appointments or tasks (food diaries, etc.) during the screening phase
• 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 weeks prior 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)