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Approximately 42% of adults in the United States (US) have obesity, with a disproportionately high prevalence in middle-aged and older adults. Individuals with obesity are at increased risk of many leading causes of morbidity and mortality in the US relative to individuals with a healthy weight. Importantly, obesity prevalence is not equally distributed across the population. Black Americans bear a greater burden of obesity, placing them at a higher risk for obesity-related diseases and mortality, compared to their non-Hispanic White and Asian/Asian American counterparts. With no broadly effective preventive or therapeutic treatments, and projections that the rate of adult obesity and obesity disparities will continue to rise, there is a critical need to better understand how to intervene on the origins of obesity and design comprehensive strategies to prevent it. Discrimination has been implicated as a social determinant of health and health disparities. Nevertheless, research on discrimination as a social determinant of obesity has, (a) yet to assess multiple forms of discrimination (neighborhood and interpersonal) simultaneously in relation to obesity and obesity disparities, (b) understudied the cellular-level processes for how discrimination gets under the skin to increase the risk of obesity, (c) not sufficiently investigated whether social integrationthat is, the level of involvement in a variety of social relationshipspotentially buffer any physiological effects of discrimination, and (d) not fully investigated the obesogenic effects of discrimination across the life course. We propose to address these critical gaps using longitudinal data on three large nationally representative cohorts to test the association between two forms of discrimination: neighborhood and interpersonal discrimination and adiposity; to evaluate the role of inflammatory gene expression as a potential mediator; and evaluate the moderating effect of social integration, which has been hypothesized to negate the health risk of discrimination. By elucidating the temporal and contextual dimensions of discrimination on adiposity, characterizing novel molecular pathways, and assessing the modulatory impact of social integration, the findings can facilitate the optimization of current obesity interventions.

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