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Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular events. However, the influence of exposure to airborne particles on the development of NAFLD is less recognised. The aim of this study was to investigate the impact of silica nanoparticles (SiNPs) on the development of liver steatosis. We used molecular and proteomic SWATH-MS methods to investigate the changes in the liver proteome of apolipoprotein E-knockout mice (<jats:italic>apoE<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice) exposed to SiNPs for 4\u00a0months in a whole-body exposure chamber. Exposure to SiNPs evoked microvesicular liver steatosis in <jats:italic>apoE<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice. Quantitative liver proteomics showed significant downregulation of ribosomal proteins and endoplasmic reticulum proteins. Gene expression analysis revealed a reduced level of proteins related to endoplasmic reticulum stress. Treatment with SiNPs decreased mitochondrial membrane potential and increased the production of reactive oxygen species in cultured HepG2 cells. This is the first report that inhalation exposure to SiNPs induces microvesicular steatosis and significant changes in the liver proteome in vivo. Our results highlight the important role of silica and point to the ER stress response and mitochondrial dysfunction as potential mechanisms responsible for the increase in fatty liver by SiNPs.<\/jats:p>","DOI":"10.1007\/s11356-022-22179-6","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T17:25:52Z","timestamp":1659115552000},"page":"699-709","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Changes in the liver proteome in apoE knockout mice exposed to inhalation of silica nanoparticles indicate mitochondrial damage and impairment of ER stress responses associated with microvesicular steatosis"],"prefix":"10.1007","volume":"30","author":[{"given":"Kamila","family":"Stachyra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kiepura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Suski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Ulatowska-Bia\u0142as","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Ku\u015b","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Wi\u015bniewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaudia","family":"Czepiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Majka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafa\u0142","family":"Olszanecki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"22179_CR1","unstructured":"Agency for Toxic Substances and Disease Registry (ATSDR), 2019. 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