Decoding Environmental Chemical Impacts on Metabolic Health through OMICs

Abstract

Metabolic disorders, a group of conditions that occur when the body's normal metabolic processes are disrupted, have emerged as a major global health problem. These conditions, which include obesity, type 2 diabetes (T2D), metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic syndrome, pose significant risks to human health and quality of life, resulting in increased morbidity and mortality (2). They are particularly concerning in vulnerable groups such as pediatric populations. This alarming trend has prompted critical research into risk factors that contribute to metabolic disorders, challenging the traditional view that attributes these disorders only to lifestyle factors such as diet and lack of physical activity. Ample evidence has been collected demonstrating that these disorders can also result from exposure to chemicals present in the environment, known as metabolism-disrupting chemicals (MDCs).

This dissertation decoded the interplay between environmental chemical exposures and metabolic disorders in pediatric populations and applied OMICs to decipher the underlying mechanisms of pathogenesis. The findings of this dissertation offer actionable insights for policymakers, regulatory bodies, and public health practitioners aiming to mitigate the adverse effects of environmental chemical exposures on metabolic health. First, the observed associations of specific chemical exposures, such as PCB-153, Cu, MEP, MBzP, and certain PFAS (i.e., PFOA, PFOS, POSF, PFNA, PFHxS), underscore the need for ongoing monitoring and targeted regulatory measures to limit their prevalence in the environment and human exposure. Second, the biomarkers discovered in this dissertation should undergo further validation in an optimized study design (e.g., large cohort over extended periods) with sufficient power, as they have the potential to offer tangible indicators for assessing metabolic disorder risks, thereby facilitating disease prevention and early intervention strategies. Essentially, this dissertation emphasized that identifying biomarkers, creating easy-to-measure indicators of health outcomes, and adopting a holistic approach to understanding and alleviating the health impacts of MDCs are imminent. Incorporating these research findings into evidence synthesis and promoting interdisciplinary collaboration would be crucial to establishing evidence-based regulations and initiatives. This, in turn, would effectively safeguard the well-being of vulnerable populations and promote healthier environments for future generations.