Polystyrene nanoplastics induce glycolipid metabolism disorder via NF-κB and MAPK signaling pathway in mice.

Autor: Fan X; School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China., Li X; School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China., Li J; School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China., Zhang Y; School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China., Wei X; School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China; State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150006, China., Hu H; Department of Medicine, Renal Electrolyte and Hypertension Division, Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia 19104, USA., Zhang B; School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China., Du H; School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China., Zhao M; School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China., Zhu R; School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China., Yang D; School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China., Oh Y; Faculty of Education, Wakayama University, Wakayama 640-8441, Japan., Gu N; School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China; State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150006, China. Electronic address: guning@hit.edu.cn.
Jazyk: angličtina
Zdroj: Journal of environmental sciences (China) [J Environ Sci (China)] 2024 Mar; Vol. 137, pp. 553-566. Date of Electronic Publication: 2023 Mar 02.
DOI: 10.1016/j.jes.2023.02.040
Abstrakt: Nanoplastics-induced developmental and reproductive toxicity, neurotoxicity and immunotoxicity are a focus of widespread attention. However, the effects of nanoplastics (NPs) on glycolipid metabolism and the precise underlying mechanisms are unclear at present. Here, we showed that oral administration of polystyrene nanoparticles (PS-NPs) disrupts glycolipid metabolism, with reactive oxygen species (ROS) identified as a potential key signaling molecule. After PS-NPs treatment, excessive production of ROS induced the inflammatory response and activated the antioxidant pathway through nuclear factor-erythroid factor 2-related factor 2. The activation of nuclear factor-κB (NFκB) signaling pathway induced the phosphorylation of the mitogen-activated protein kinases (MAPK) signaling pathway, which induced the activation of extracellular regulated kinases (ERK) and p38. Constitutive activation of the MAPK signaling proteins induced high continued phosphorylation of insulin receptor substrate-1, in turn, leading to decreased protein kinase B (Akt) activity, which weakened the sensitivity of liver cells to insulin signals and induced insulin resistance. In parallel, phosphorylation of Akt led to loss of control of FoXO1, a key gene of gluconeogenesis, activating transcription of glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase (PEPCK) in a manner dependent on PGC1α. Moreover, the activated ERK promoted lipid accumulation through ERK-PPARγ cascades. Therefore, sterol regulatory element-binding protein-1 and levels of its downstream lipogenic enzymes, ACC-1, were up-regulated. Upon treatment with the antioxidant resveratrol, PS-NPs-induced glucose and lipid metabolic disorders were improved by inhibiting ROS-induced activation of NFκB and MAPK signaling pathway in mice. Based on above, PS-NPs exposure disrupts glycolipid metabolism in mice, with ROS identified as a potential key signaling molecule.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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