2573-P: Polystyrene Microplastics Exposure Exacerbates Thyroid–Brown Adipose Tissue Axis Dysregulation to Promote Obesity and Glucose–Lipid Metabolic Disorders

Introduction and Objective: The global prevalence of obesity and diabetes has escalated dramatically in recent decades, driven by both obesogenic dietary patterns (e.g., high-fat diet, HFD) and environmental contaminants such as microplastics (MPs). However, the combined effects of chronic low-dose MPs exposure and HFD consumption on the progression of metabolic diseases remain poorly understood. This study aims to investigate the role of polystyrene microplastics (PS-MPs) in exacerbating HFD-induced metabolic dysfunction and its underlying mechanisms. Methods: Male C57BL/6J mice were randomized into four groups: normal chow diet (NCD), NCD + PS-MPs, HFD, and HFD + PS-MPs. PS-MPs (25-30 μg/kg body weight/day) was administered via oral gavage for 14-16 weeks. Metabolic parameters including body weight gain, energy expenditure, body fat composition, glucose tolerance, insulin sensitivity, and thyroid function were systematically evaluated. Results: PS-MPs exposure significantly exacerbated HFD-induced obesity and metabolic disorders, characterized by accelerated weight gain, reduced energy metabolism, impaired glucose homeostasis, and dysregulated lipid profiles. Mechanistically, in vivo and in vitro experiments confirmed that low-dose PS-MPs primarily disrupt the thyroid-brown adipose tissue (BAT) axis to mediate these adverse effects. Notably, thyroid hormone supplementation reversed the metabolic impairments, further validating the causal role of the thyroid-BAT axis in PS-MPs-induced metabolic dysfunction. Conclusion: These findings highlight the critical contribution of chronic low-dose PS-MPs exposure to the pathogenesis of obesity and diabetes, particularly in the context of pre-existing metabolic stress (e.g., HFD). The identification of the thyroid-BAT axis as a key mediator provides novel therapeutic targets for mitigating metabolic diseases associated with environmental MPs exposure. Disclosure G. Wei: None. F. Shen: None. F. Ma: None. W. Cao: None. J. Yang: None.