This study will be the first clinical trial to examine the impact of two different weight loss interventions on novel mechanisms that promote obesity and impede its successful treatment, including cognitive function and self-regulatory factors. The results will provide important data about how impaired cognitive function and/or self-regulation promote obesity and how different weight loss treatments may differentially impact these factors; this information will be used to identify promising cognitive and self-regulatory treatment targets for preventing further obesity development and for maintaining weight loss.

This K23 award will allow Dr. Misty Hawkins, a clinical psychologist with expertise in behavioral medicine and obesity, to further develop into an independent investigator proficient in physiological, neuropsychological, and self-regulatory research methods and interventions that will allow her to study novel mechanisms of and treatments for obesity maintenance. She has a career interest in intervening on the neuropsychological factors related to obesity. Her research goal is to identify novel cognitive and self-regulatory mechanisms of obesity in this pilot trial which can then be targeted in larger randomized controlled trials (RCTs) to reduce obesity development or to maintain weight loss. Obesity continues to be a global epidemic, yet successful interventions for obesity are rare, with 80% of individuals in treatment programs being unsuccessful at achieving long-term weight loss. The training and research activities in this K23 application will allow her to examine the complexities of physiological dysregulation, cognitive deficits, and self-regulatory failure in an obesity treatment study. The application proposes an intensive, 5-year program of mentored research and formal training activities to enhance Dr. Hawkins' skills and experience in: 1) basic research on and assessment of cognitive function; (2) assessment of obesity-related physiological changes; (3) research with patient populations; (4) advanced assessment of self-regulation (SR); and (5) the conduct of randomized clinical trials and advanced statistics. In the long term, Dr. Hawkins will apply these translational research skills to study targeted cognitive and self-regulation interventions as potentially effective treatments for persons with obesity who may exhibit cognitive deficits or chronic self-regulatory failure. The research component of this career development award is a clinical trial examining the impact of two different weight loss treatments on physiological markers, cognition, self-regulation, and health behaviors in 96 obese persons. The specific aims are to: 1) Confirm that baseline obesity-related physiological dysregulation is linked to cognitive deficits, poorer self-regulation, and obesogenic behaviors, 2) Demonstrate that the two treatment groups have improvements in biomarkers, cognition, SR, and obesogenic behaviors, less weight gain, and greater weight loss, and 3) Evaluate whether the acceptance-based treatment (ABT) group has greater improvements in biomarkers, cognition, SR, and obesogenic behaviors, less weight gain, and greater weight loss than the standard behavioral treatment group (SBT) from pre- to post-treatment and 1-year follow-up. Oklahoma State University and its research partner Oklahoma University Health Sciences Center provide exceptional environments for Dr. Hawkins to gain the skills needed to achieve her goals. The training component uses academic resources including the College of Arts and Sciences and the Department of Psychology. Dr. Hawkins' mentors are highly regarded scientists in the areas of obesity, neuropsychology, psychophysiology, nutrition, and patient-oriented research.

**An open trial arm of ABT was added to the study in September 2016 to test feasibility of ABT among members of Cherokee Nation. This arm is entitled POWER-UP: Pilot Of WEight Reduction in Underserved Populations. Glucose is the only biomarker being measured in POWER-UP.

Inclusion Criteria:

• >21 years old
• <65 years old
• BMI > 27
• BMI < 52
• Attended Information/Recruitment session
• **For Cherokee Nation arm of the study only, participants must endorse Native American/American Indian racial identity (POWER-UP).

Exclusion Criteria:

• Age out of stated range
• BMI out of stated range
• Physician says physical activity is contraindicated (won't sign off) or participant meets the criteria on the Physical Activity Readiness Questionnaire (PARQ) for need a physician signature and doesn't obtain one.
• History of bariatric surgery or planning to get surgery over next 12 months
• Pregnant, planning to become pregnant over next 12 months
• Currently breastfeeding
• Failure of Independence (a family member/friend enrolling in study)
• History or current serious eating disorder pathology
• Current severe depression or suicidal ideation
• Current severe anxiety
• History or current substance use disorder
• History of hypomanic or manic episode
• History of psychotic episode
• History of neurological disorder or head injury (e.g., stroke, epilepsy, loss of consciousness >10 min)
• Recent significant weight loss
• Current Type I Diabetes
• Medications or disease that impact weight (e.g., mirtazapine, prednisone, dexamethasone, dronabinol, megestrol, Cushing's syndrome). The exclusion of persons with hypothyroidism was discontinued given very high base rates in recruitment sample. We will run sensitivity analyses by those with and without hypothyroidism.