PROJECT SUMMARY/ABSTRACT Persons with a higher body weight (i.e., obesity) face pervasive and persistent stigma. Many individuals internalize negative societal messages and stereotypes about weight, leading to self-directed stigmatization. Internalized weight stigma is associated with impaired mental health, but little is known about its effects on physical health. Prior preliminary data suggest that adults with obesity who internalize weight stigma to a high degree may have greater vulnerability to the metabolic syndrome (MetS) than those who do not. This may be due to the chronic stress of constant self-disparagement among individuals who internalize weight stigma and, as a result, dysregulation of the inflammatory-immune response. Identifying the contribution of internalized weight stigma to cardiovascular disease (CVD) risk and stress-induced inflammation is critical to advancing knowledge of the health effects of stigma and to enhancing the treatment of obesity. The current study aims to determine the relationship between internalized weight stigma and MetS above and beyond the effects of body mass index (BMI), depression, and demographic characteristics. The study will also explore whether internalized weight stigma is associated with heightened levels of the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and myeloperoxidase (MPO). This will be a cross-sectional, observational study of 110 postmenopausal women with obesity (BMI ≥ 30 kg/m2) who report either high or low levels of internalized weight stigma, as determined by cutoff scores on the Weight Bias Internalization Scale. Eligible participants will attend a single blinded assessment visit, which will include: measurement of height, weight, blood pressure, and waist circumference; fasting blood draw to assess glucose, triglycerides, high-density lipoprotein cholesterol, CRP, IL-6, and MPO; and assessment by interview of current medications, diagnoses, and infections. Participants will also complete online questionnaires that assess depression and other relevant psychosocial measures. The primary analysis will determine whether participants who report high versus low internalized stigma have significantly greater odds of meeting criteria for MetS. Secondary analyses will explore the relationship between internalized weight stigma and CRP, IL-6, and MPO, respectively. All analyses will control for BMI, depression, and demographic characteristics. The proposed study builds on the K23 award project, which is a randomized controlled trial that tests the effects on long-term weight loss of a psychological intervention designed to reduce internalized weight stigma, combined with weight loss treatment, compared to weight loss treatment alone. This study will extend the K23 award focus on cardiometabolic health by providing novel data that isolate the contribution of internalized weight stigma to inflammation and CVD risk, independent of body weight. Data will be used t...