6PPD-quinone (6PPDQ), a derivative of the antioxidant 6PPD used in the rubber industry, has been implicated in environmental and public health risks. To explore its impact on metabolic and cognitive functions, we orally administered 6PPDQ to mice and assessed its effects. Our results show that 6PPDQ induces a dose-dependent increase in body weight, elevated fasting blood glucose, insulin resistance, and other hallmarks of metabolic syndrome. Furthermore, cognitive tests revealed significant impairments in learning and memory in 6PPDQtreated mice. Transcriptomic and Western blot analyses suggest that 6PPDQ disrupts insulin signaling through inhibition of the PI3K-AKT pathway, leading to metabolic and cognitive dysfunction. Notably, treatment with the PI3K-AKT agonist SC79 partially alleviated these effects. These findings highlight the health risks of 6PPDQ exposure and suggest potential avenues for preventive and therapeutic strategies.
基金：
Jiangsu Natural Science Foundation Project [BK20191142]; Scientific Research Project of the Jiangsu Provincial Health Commission [M2024075]; High-level Talent Training Project of the Wuxi Taihu Talent Plan [BJ2020055, BJ2023048]; Clinical Medical Research Project of the Affiliated Hospital of Jiangnan University [LCYJ202321]; Jiangsu Province Clinical Key Speciality Funding [3631608ZKJS]; Post-graduate Research & Practice Innovation Program of Jiangsu Province [KYCX24_2648]
第一作者机构：[1]Jiangnan Univ, Affiliated Hosp, Wuxi 214122, Peoples R China[2]Jiangnan Univ, Wuxi Med Coll, Wuxi 214122, Peoples R China[3]Shanghai Jiao Tong Univ, Sch Med, Tongren Hosp, Shanghai 200336, Peoples R China
通讯作者：
通讯机构：[1]Jiangnan Univ, Affiliated Hosp, Wuxi 214122, Peoples R China[2]Jiangnan Univ, Wuxi Med Coll, Wuxi 214122, Peoples R China
推荐引用方式(GB/T 7714)：
Wang Leisheng,Fu Yifei,Xu Shiwei,et al.Targeting the PI3K-AKT pathway to alleviate 6PPDQ-induced cognitive impairment associated with metabolic syndrome[J].ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY.2025,302:doi:10.1016/j.ecoenv.2025.118711.
APA：
Wang, Leisheng,Fu, Yifei,Xu, Shiwei,Chen, Enhong,Zhang, Shuo...&Hu, Hao.(2025).Targeting the PI3K-AKT pathway to alleviate 6PPDQ-induced cognitive impairment associated with metabolic syndrome.ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,302,
MLA：
Wang, Leisheng,et al."Targeting the PI3K-AKT pathway to alleviate 6PPDQ-induced cognitive impairment associated with metabolic syndrome".ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 302.(2025)
