PMID- 37980039 OWN - NLM STAT- MEDLINE DCOM- 20231127 LR - 20231127 IS - 1001-0742 (Print) IS - 1001-0742 (Linking) VI - 137 DP - 2024 Mar TI - Polystyrene nanoplastics induce glycolipid metabolism disorder via NF-kappaB and MAPK signaling pathway in mice. PG - 553-566 LID - S1001-0742(23)00087-6 [pii] LID - 10.1016/j.jes.2023.02.040 [doi] AB - 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-kappaB (NFkappaB) 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 PGC1alpha. Moreover, the activated ERK promoted lipid accumulation through ERK-PPARgamma 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 NFkappaB 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. CI - Copyright (c) 2023. Published by Elsevier B.V. FAU - Fan, Xingpei AU - Fan X AD - School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China. FAU - Li, Xiaoyan AU - Li X AD - School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China. FAU - Li, Jiaxin AU - Li J AD - School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China. FAU - Zhang, Yuxia AU - Zhang Y AD - School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China. FAU - Wei, Xiangjuan AU - Wei X AD - 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. FAU - Hu, Hailong AU - Hu H AD - Department of Medicine, Renal Electrolyte and Hypertension Division, Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia 19104, USA. FAU - Zhang, Boya AU - Zhang B AD - School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China. FAU - Du, Haining AU - Du H AD - School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China. FAU - Zhao, Meimei AU - Zhao M AD - School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China. FAU - Zhu, Ruijiao AU - Zhu R AD - School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China. FAU - Yang, Daqian AU - Yang D AD - School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China. FAU - Oh, Yuri AU - Oh Y AD - Faculty of Education, Wakayama University, Wakayama 640-8441, Japan. FAU - Gu, Ning AU - Gu N AD - 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. LA - eng PT - Journal Article DEP - 20230302 PL - Netherlands TA - J Environ Sci (China) JT - Journal of environmental sciences (China) JID - 100967627 RN - 0 (NF-kappa B) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - 0 (Polystyrenes) RN - 0 (Microplastics) RN - 0 (Reactive Oxygen Species) RN - 0 (Antioxidants) RN - 0 (Lipids) SB - IM MH - Mice MH - Animals MH - *NF-kappa B/metabolism/pharmacology MH - Proto-Oncogene Proteins c-akt/metabolism/pharmacology MH - Mitogen-Activated Protein Kinases/metabolism/pharmacology MH - Polystyrenes/toxicity MH - Microplastics MH - Reactive Oxygen Species/metabolism MH - Antioxidants MH - Signal Transduction MH - *Metabolic Diseases MH - Lipids/pharmacology OTO - NOTNLM OT - Hyperglycemia OT - Inflammatory response OT - Lipid metabolism OT - Nanoplastics OT - Reactive oxygen species (ROS) OT - Resveratrol COIS- 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. EDAT- 2023/11/19 09:42 MHDA- 2023/11/27 12:44 CRDT- 2023/11/18 20:59 PHST- 2022/09/12 00:00 [received] PHST- 2023/02/20 00:00 [revised] PHST- 2023/02/21 00:00 [accepted] PHST- 2023/11/27 12:44 [medline] PHST- 2023/11/19 09:42 [pubmed] PHST- 2023/11/18 20:59 [entrez] AID - S1001-0742(23)00087-6 [pii] AID - 10.1016/j.jes.2023.02.040 [doi] PST - ppublish SO - J Environ Sci (China). 2024 Mar;137:553-566. doi: 10.1016/j.jes.2023.02.040. Epub 2023 Mar 2.