@article{6e38374d36814cada3c72190ace66f99,
title = "Long-term exposure to titanium dioxide nanoparticles promotes diet-induced obesity through exacerbating intestinal mucus layer damage and microbiota dysbiosis",
abstract = "Titanium dioxide nanoparticles (TiO2-NPs) are commonly used as food additives, including some high-fat foods that are risk factors for obesity. However, little is known about the effects of chronic TiO2-NPs digestion in the population on high fat diet (HFD). Herein, we reported that TiO2-NPs exacerbated HFD-induced obesity by disruption of mucus layer and alterations of gut microbiota. Oral intake of TiO2-NPs significantly increased body weight, liver weight, and amount of adipose tissues, especially in HFD-fed mice. Mechanistic studies revealed TiO2-NPs induced colonic mucus layer disruption and obesity-related microbiota dysbiosis. The damage on mucus was demonstrated through down-regulation of Muc2 gene and the absorption of mucin protein by TiO2-NPs. Consequently, mucus layer damage combined microbiota dysbiosis escalated the low-grade systemic inflammation, which exacerbated HFD-induced obesity. In contrast, gut microbiota depletion eliminated these effects, indicating gut microbiota were necessary for TiO2-NPs-induced inflammation and obesity. All the results stated the alarming role of TiO2-NPs in the HFD-driven obesity and emphasized the reevaluating the health impacts of nanoparticles commonly used in daily life, particularly, in susceptible population. [Figure not available: see fulltext.]",
keywords = "gut microbiota, mucus layer, nanosafety, obesity, titanium dioxide nanoparticles",
author = "Xiaoqiang Zhu and Lijun Zhao and Zhi Liu and Qibing Zhou and Yanhong Zhu and Yuliang Zhao and Xiangliang Yang",
note = "Funding Information: This work was supported by the National Natural Science Foundation of China (Nos. 81573013 and 81627901) and the National Key Research and Development Program of China (2018YFA0208903). We thank the Research Core Facilities for Life Science (RCFLS), Huazhong University of Science and Technology for its technical support and services. Author contributions: X. L. Y. and Y. L. Z. managed the project and guided the research. X. Q. Y. and Y. H. Z. conceived the idea and designed the research. X. Q. Y. carried out characterization of TiO-NPs. X. Q. Z. and L. J. Z. performed all animal experiments and tissue section staining experiments including H&E, PAS, Alcian blue staining and immunohistochemistry. RT-PCR assays, ELISA assays and enema experiment in vitro were done by X. Q. Z., X. Q. Z., Y. H. Z., and L. J. Z. analyzed all the data. X. Q. Z., Y. H. Z., and Q. B. Z. wrote the manuscript. The authors declare that they have no conflict of interest. 2 Funding Information: This work was supported by the National Natural Science Foundation of China (Nos. 81573013 and 81627901) and the National Key Research and Development Program of China (2018YFA0208903). We thank the Research Core Facilities for Life Science (RCFLS), Huazhong University of Science and Technology for its technical support and services. Author contributions: X. L. Y. and Y. L. Z. managed the project and guided the research. X. Q. Y. and Y. H. Z. conceived the idea and designed the research. X. Q. Y. carried out characterization of TiO2 -NPs. X. Q. Z. and L. J. Z. performed all animal experiments and tissue section staining experiments including H&E, PAS, Alcian blue staining and immunohistochemistry. RT-PCR assays, ELISA assays and enema experiment in vitro were done by X. Q. Z., X. Q. Z., Y. H. Z., and L. J. Z. analyzed all the data. X. Q. Z., Y. H. Z., and Q. B. Z. wrote the manuscript. The authors declare that they have no conflict of interest. Publisher Copyright: {\textcopyright} 2020, Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature.",
year = "2021",
month = may,
doi = "10.1007/s12274-020-3210-1",
language = "English (US)",
volume = "14",
pages = "1512--1522",
journal = "Nano Research",
issn = "1998-0124",
publisher = "Tsinghua University Press",
number = "5",
}