Assessing the impact of exogenous stressors on obesity and pro-inflammatory gene expression

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 currently have obesity. Yet, we still have an inadequate understanding of the etiology of obesity and the upstream drivers that contribute to its development and persistence. Exogenous stress, operating at both interpersonal and residential levels, has been implicated as a potential obesogenic factor. However, the relationship between multiple forms of exogenous stress and adiposity remains understudied. Moreover, the cellular and molecular processes through which such exposures affect physiological function and contribute to excess weight gain are not well understood. This study aims to define the relationship between multiple forms of exogenous stress and adiposity, as well as downstream markers of inflammation, in order to inform prevention and treatment strategies that can reduce obesity across the population. Using 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 residential- and interpersonal-level stress and adiposity indicators (i.e., body mass index and waist circumference). We will then examine whether these exposures are associated with alterations in leukocyte gene expression profiles related to inflammatory pathways, identify relevant cellular and molecular mechanisms, and test whether gene expression mediates the relationship between exogenous stress and adiposity. Finally, we will evaluate the moderating effect of network engagement on these associations. This project will lay the groundwork for future research on exogenous stress and age-related health outcomes, and inform strategies to promote healthier metabolic functioning across the life course.