Abstract Obesity has been a persistent public health issue for decades. People with obesity experience higher risk of chronic diseases, such as diabetes, chronic kidney disease, hypertension, coronary heart disease, and stroke. Approximately 42% of adults in the United States (US) currently have obesity, with a disproportionately high prevalence among Black Americans. Yet, we still have an inadequate understanding of the etiology of obesity and the drivers of obesity disparities. Discrimination has been implicated as an obesogenic risk factor. Discrimination is understood as a multidimensional construct that operate at multiple levels and in different social contexts. Yet, the association between multiple forms of discrimination and adiposity is not well understood. It also remains understudied the cellular-level processes for how discrimination “gets under the skin” to produce physiological dysregulation. Defining the relationship between multiple forms of discrimination and adiposity and molecular markers of inflammation will provide the foundation for increasing the efficacy of prevention efforts and treatment to reduce obesity and Black-White obesity disparities. Using the data from three large, population-based cohort studies—the National Longitudinal Study of Adolescent to Adult Health, Midlife in the United States, and Health and Retirement Study—we will first assess the associations between multiple forms of discrimination (i.e., neighborhood and interpersonal) with adiposity markers (i.e., body mass index and waist circumference). We will then assess the association between multiple forms of discrimination with downstream changes in cellular gene expression of inflammation, identify cellular and molecular mechanisms involved, and quantify the extent to gene expression mediate the relationship between discrimination and adiposity. We will also quantify the extent to which discrimination explain racial disparities in adiposity and gene expression. Lastly, we will evaluate the moderating effect of social integration on the associations between discrimination and adiposity and gene expression. The project will lay the groundwork for future studies to assess the association between discrimination and other age-related outcomes and inform interventions that can be developed to reduce disparities in health.