Effects of Obesogenic Environment and Stress Hormone on Neuroinflammation

INTRODUCTION: Obesity is a pervasive health issue with profound implications for both metabolic and mental health. Psychosocial stress can exacerbate susceptibility to obesity, with neuroinflammation posited as a critical mediator of this relationship. However, the molecular mechanisms driving this vulnerability remain poorly understood. This study aims to elucidate the interplay between an obesogenic environment and stress hormones on neuroimmune function. METHODS: Human microglia cells (HMC3) were exposed to palmitate and hydrocortisone for 24 hours to investigate their combined effects on cytokine release, reactive oxygen species (ROS) production, and activation of inflammatory pathways. Tumor necrosis factor-alpha (TNF-α) levels were quantified using ELISA, while FKBP5 and TNF-α gene expression were assessed via real-time PCR. ROS production was measured using the MUSE Oxidative Stress kit, and NF-κB activation was evaluated using a Transcription Factor Assay Kit. RESULTS: Microglia cells showed increase number and proinflammatory phenotype in response to an obesogenic environment (palmitate). TNF-α were overproduced in response to palmitate and stress (hydrocortisone) (p = 0.0002, n=4). FKBP5 gene expression was decrease by palmitate (p < 0.0001, n=4). The combined treatment with palmitate and hydrocortisone synergistically enhanced ROS production in HMC3 cells (p < 0.0001, n = 4) and significantly activated NF-κB pathways (p < 0.01, n = 4). CONCLUSIONS: Chronic exposure to an obesogenic diet disrupts microglial function and amplifies neuroinflammatory responses. The synergistic effects of stress hormones and an obesogenic environment further exacerbate oxidative stress and inflammation. These findings shed light on the mechanisms by which stress and obesity may contribute to heightened neuroinflammation, potentially influencing stress reactivity and obesity-related behaviors. Understanding these interactions could inform therapeutic strategies targeting neuroinflammatory pathways. Partial funding for this study was provided by the NIH (DK124727, GM060507, MD006988) and the San Juan Bautista School of Medicine Pilot Projects Program awarded to YIN. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.