Compulsive overeating afflicts 30% of treatment-seeking individuals with obesity and correlates with cardiovascular disease (CVD) risk factors. Current obesity intervention approaches, however, do not specifically target mechanisms that underlie compulsive overeating. My research on obese women shows that compulsive overeating is associated with alterations in endogenous opioid activity as indexed by nausea (an opioidergic withdrawal symptom) following administration of the opioid antagonist naltrexone (NX). Data also show associations between compulsive overeating, highly palatable food intake, impulsivity, reward-sensitivity, and other factors, which, taken together, may characterize a compulsive overeating phenotype in obesity. This K23 Award will support the development of my independent research career focused on more effective interventions for compulsive overeating in obesity and its cardiovascular comorbidities. The proposed experimental medicine studies will advance this research program by investigating a compulsive overeating phenotype in obesity using: (1) a multimethod assessment battery (MAB) to assess behavioral, psychological, and nutritional correlates of obesity, (2) obesity-related indices of CVD risk (e.g., glycemic control, hypertension), and (3) my novel NX protocol to assess altered endogenous opioid activity (Aim 1). I will assess NX protocol test-retest reliability and, in a subset of participants who do not have a NX response (nausea) at initial testing, test whether NX response can be induced after administering our 2-week sugar-beverage consumption protocol, as sugar impacts endogenous opioid activity (Aim 2). With my mentors, I will identify intervention targets in compulsive overeating based on Study 1 results and a current review of the literature. I will then select intervention components that have produced change in these targets in prior research, and will develop, refine, and test these components in a pilot study of women with compulsive overeating and obesity (Aim 3). I will examine feasibility and acceptability of the intervention components and collect pilot data on pre- post change in the measures used in Study 1. Pilot data will inform the R34 Clinical Trial Pilot Study proposal I will submit to test an optimized intervention for compulsive overeating in obesity. The proposed training plan will provide me with the support and mentorship necessary to gain expertise in the identification of opioidergic, psychological, behavioral, and nutritional targets associated with compulsive overeating; to obtain the training needed to independently design and conduct laboratory research and to assess obesity-related CVD risk factors; and to obtain the training necessary to develop and test obesity interventions. These training experiences, coupled with the proposed research plan, will facilitate my career devoted to the development of interventions that act on mechanisms underlying compulsive overeating in obesity. This K23 Award will deepen current understanding and treatment of compulsive overeating in obesity and promote development of interventions for this distinct subset of individuals, for whom we currently lack effective interventions.

Public Health Relevance

Obesity is an important predictor of cardiovascular disease and early mortality, and compulsive overeating has been identified as an independent contributor to poor metabolic health and weight gain. These studies will identify a compulsive overeating subtype in obesity using psychological, behavioral, nutritional, and metabolic measures, as well as a new method of assessing activity of the body's natural opiate system, which interacts with eating behavior. I will test a pilot intervention to improve these measures in individuals with obesity, and results will lead to development of more effective interventions for compulsive overeating in obesity.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL133442-02
Application #
9331724
Study Section
NHLBI Mentored Patient-Oriented Research Review Committee (MPOR)
Program Officer
Nicastro, Holly L
Project Start
2016-08-15
Project End
2021-07-31
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
Brewer, Judson A; Ruf, Andrea; Beccia, Ariel L et al. (2018) Can Mindfulness Address Maladaptive Eating Behaviors? Why Traditional Diet Plans Fail and How New Mechanistic Insights May Lead to Novel Interventions. Front Psychol 9:1418
Cummings, Jenna R; Mason, Ashley E; Puterman, Eli et al. (2018) Comfort Eating and All-Cause Mortality in the US Health and Retirement Study. Int J Behav Med 25:473-478
Mason, Ashley E; Schleicher, Samantha; Coccia, Michael et al. (2018) Chronic Stress and Impulsive Risk-Taking Predict Increases in Visceral Fat over 18 Months. Obesity (Silver Spring) 26:869-876
Mason, Ashley E; Saslow, Laura; Moran, Patricia J et al. (2018) Examining the Effects of Mindful Eating Training on Adherence to a Carbohydrate-Restricted Diet in Type 2 Diabetes: the DELISH Study Protocol. JMIR Res Protoc :
Mason, Ashley E; Hecht, Frederick M; Daubenmier, Jennifer J et al. (2018) Weight Loss Maintenance and Cellular Aging in the Supporting Health Through Nutrition and Exercise Study. Psychosom Med 80:609-619
Stanhope, K L; Goran, M I; Bosy-Westphal, A et al. (2018) Pathways and mechanisms linking dietary components to cardiometabolic disease: thinking beyond calories. Obes Rev 19:1205-1235
Mason, Ashley E; Jhaveri, Kinnari; Cohn, Michael et al. (2018) Testing a mobile mindful eating intervention targeting craving-related eating: feasibility and proof of concept. J Behav Med 41:160-173
Saslow, Laura; Mason, Ashley E; Kim, Sarah et al. (2018) Authors' Reply: Comment on ""An Online Intervention Comparing a Very Low-Carbohydrate Ketogenic Diet and Lifestyle Recommendations Versus a Plate Method Diet in Overweight Individuals With Type 2 Diabetes: A Randomized Controlled Trial"". J Med Internet Res 20:e181
Saslow, Laura R; Mason, Ashley E; Kim, Sarah et al. (2017) An Online Intervention Comparing a Very Low-Carbohydrate Ketogenic Diet and Lifestyle Recommendations Versus a Plate Method Diet in Overweight Individuals With Type 2 Diabetes: A Randomized Controlled Trial. J Med Internet Res 19:e36
Heshmati, Saeideh; Sbarra, David A; Mason, Ashley E (2017) The contemptuous separation: Facial expressions of emotion and breakups in young adulthood. Pers Relatsh 24:453-469

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