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

Inclusion criteria

• Age: 25 - \<60 years
• BMI: 30 - \<40 kg/m2 at the first screening visit
• Within 5% of current weight, for the past 6 months at the first screening visit
• Able to participate in ergometry testing
• Has a smart phone, tablet or computer with access to the internet

Exclusion criteria

• If 25-29 years old, \> 5% deviation from maximum weight (excluding weights while pregnant) since age 25 years
• 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
• History of pulmonary embolus in the past 6 months
• Cardiovascular disease (e.g. myocardial infarction, stroke, hospitalization for unstable angina, or transient ischemic attack) within the past 6 months
• Current major depressive disorder or history of major depressive disorder within 2 years
• Any regular tobacco or nicotine use in the past year
• Currently engaging in intense physical training or training for a sports event including, but not limited to, a marathon or body building
• Currently pregnant, or less than one-year post-partum or actively planning to become pregnant within the next two years
• Presently classified as being in New York Heart Association Class II or greater or dysrhythmia
• Diabetes (type 1 or 2 - HbA1c ≥ 6.5%, fasting glucose ≥ 126 mg/dL) or currently taking a glucose lowering medication
• Thyroid disease requiring hormones or medication or TSH \< 0.5 or \> 5 mIU/L
• Renal disease requiring dialysis
• Known HIV infection
• ALT or AST greater than 5 times the upper limit of normal or active gall bladder disease
• Significant anemia (Hgb \< 10 g/dL) or thrombocytopenia (platelet count \< 60,000 /mm3)
• 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)
• 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
• Current or past history of anorexia nervosa or bulimia nervosa
• Current or past diagnosis of binge eating disorder
• Diagnosis of other severe psychiatric disorder (e.g. schizophrenia, bipolar disorder)
• Unwillingness to abstain from marijuana/cannabis use for 3 weeks at each of the four assessment time points
• Known or suspected abuse or misuse of alcohol, prescription drugs, or recreational drugs
• Antiretroviral therapy (ART), including treatment for HIV, pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) within the past 3 months
• 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)
• Currently taking anticoagulant medication
• Currently enrolled in a supervised weight reduction program
• Prior or planned bariatric surgery, endoscopic therapy, device-based therapy for obesity, liposuction, cryolipolysis, or abdominoplasty
• 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
• Current celiac or diagnosed gluten intolerance or inflammatory bowel disease requiring specialized diet
• Night or rotating shift worker
• Known severe allergy (e.g. anaphylaxis) to nuts or other foods
• Systolic blood pressure (BP) \<90 mmHg and/or diastolic BP \<60 mmHg on 2 measurements during the clinical screening visit.
• 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.
• Metal implants, piercings that cannot be removed, or metal-based tattoos or hair treatments
• Exceeds limitations to fit dual-energy X-ray absorptiometry (DXA) field of view
• Known allergy to lidocaine or acetaminophen
• Non-compliance with appointments or tasks (food diaries, etc.) during the screening phase
• Blood clotting disorder or INR \> ULN or PT \> ULN or (a)PTT \> ULN
• Tendency to form thick or raised scars
• 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
• At high risk for suicide, as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)