Frontiers in pharmacology · 2025
CPT1 deficiency blocks autophagic flux to promote lipid accumulation induced by co-exposure to polystyrene microplastic and cadmium.
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Chen Zhixuan, Qu Huayi, Sun Jian, Wang Tao, Yuan Yan, Gu Jianhong, Bian Jianchun, Liu Zongping, Zou Hui
Аннотация
INTRODUCTION: Cadmium (Cd) and polystyrene microplastics (PS-MPs), two ubiquitous environmental contaminants, produce unique synergistic toxicity when co-existing. Key unanswered questions include specific effects on liver function and potential mechanisms.
METHODS: In this study, C57BL/6 mice and AML12 cells were used to establish in vivo and in vitro models to elucidate the effects of combined exposure to PS-MPs and Cd on the liver and their mechanisms.
RESULTS: The results showed that the combined effects of PS-MPs and Cd caused significantly more liver damage than exposure alone. As observed by transmission electron microscopy (TEM), the number of autophagosomes was significantly increased in the PS-MPs and Cd co-treated group. In addition, autophagic flux was assayed by RFP-GFP-LC3, a reporter system expressing dual fluorescent proteins, which showed an overwhelming enhancement of autophagic flux damage by co-exposure to PS-MPs and Cd compared to exposure alone. To further investigate the involvement of carnitine palmitoyltransferase1(CPT1) in liver injury induced by co-exposure to Cd and PS-MPs, we co-exposed Baicalin, an activator of CPT1, with PS-MPs and Cd, and showed that activation of CPT1 alleviated the impairment of autophagic fluxes induced by co-exposure of Cd and PS-MPs and further alleviated the changes in lipid accumulation and associated protein levels.
DISCUSSION: In conclusion, the concurrent exposure of PS-MPs and Cd resulted in the blockage of hepatic lipid accumulation and autophagic pathway and further aggravated the toxic damage to the liver. Activation of CPT1 could alleviate the PS-MPs and Cd-induced lipid accumulation and autophagy pathway blockage thus reducing liver injury.
METHODS: In this study, C57BL/6 mice and AML12 cells were used to establish in vivo and in vitro models to elucidate the effects of combined exposure to PS-MPs and Cd on the liver and their mechanisms.
RESULTS: The results showed that the combined effects of PS-MPs and Cd caused significantly more liver damage than exposure alone. As observed by transmission electron microscopy (TEM), the number of autophagosomes was significantly increased in the PS-MPs and Cd co-treated group. In addition, autophagic flux was assayed by RFP-GFP-LC3, a reporter system expressing dual fluorescent proteins, which showed an overwhelming enhancement of autophagic flux damage by co-exposure to PS-MPs and Cd compared to exposure alone. To further investigate the involvement of carnitine palmitoyltransferase1(CPT1) in liver injury induced by co-exposure to Cd and PS-MPs, we co-exposed Baicalin, an activator of CPT1, with PS-MPs and Cd, and showed that activation of CPT1 alleviated the impairment of autophagic fluxes induced by co-exposure of Cd and PS-MPs and further alleviated the changes in lipid accumulation and associated protein levels.
DISCUSSION: In conclusion, the concurrent exposure of PS-MPs and Cd resulted in the blockage of hepatic lipid accumulation and autophagic pathway and further aggravated the toxic damage to the liver. Activation of CPT1 could alleviate the PS-MPs and Cd-induced lipid accumulation and autophagy pathway blockage thus reducing liver injury.