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Dietary Nano-ZnO Is Absorbed via Endocytosis and ZIP Pathways, Upregulates Lipogenesis, and Induces Lipotoxicity in the Intestine of Yellow Catfish
Nano-sized zinc oxide (nano-ZnO) affects lipid deposition, but its absorption patterns and mechanisms affecting lipid metabolism are still unclear. This study was undertaken to investigate the molecular mechanism of nano-ZnO absorption and its effects on lipid metabolism in the intestinal tissues of...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584588/ https://www.ncbi.nlm.nih.gov/pubmed/34769475 http://dx.doi.org/10.3390/ijms222112047 |
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author | Chen, Shu-Wei Lv, Wu-Hong Wu, Kun Chen, Guang-Hui Chen, Fang Song, Chang-Chun Luo, Zhi |
author_facet | Chen, Shu-Wei Lv, Wu-Hong Wu, Kun Chen, Guang-Hui Chen, Fang Song, Chang-Chun Luo, Zhi |
author_sort | Chen, Shu-Wei |
collection | PubMed |
description | Nano-sized zinc oxide (nano-ZnO) affects lipid deposition, but its absorption patterns and mechanisms affecting lipid metabolism are still unclear. This study was undertaken to investigate the molecular mechanism of nano-ZnO absorption and its effects on lipid metabolism in the intestinal tissues of a widely distributed freshwater teleost yellow catfish Pelteobagrus fulvidraco. We found that 100 mg/kg dietary nano-ZnO (H-Zn group) significantly increased intestinal Zn contents. The zip6 and zip10 mRNA expression levels were higher in the H-Zn group than those in the control (0 mg/kg nano-ZnO), and zip4 mRNA abundances were higher in the control than those in the L-Zn (50 mg/kg nano-ZnO) and H-Zn groups. Eps15, dynamin1, dynamin2, caveolin1, and caveolin2 mRNA expression levels tended to reduce with dietary nano-ZnO addition. Dietary nano-ZnO increased triglyceride (TG) content and the activities of the lipogenic enzymes glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), and isocitrate dehydrogenase (ICDH), upregulated the mRNA abundances of lipogenic genes 6pgd, fatty acid synthase (fas), and sterol regulatory element binding protein 1 (srebp1), and reduced the mRNA expression of farnesoid X receptor (fxr) and small heterodimer partner (shp). The SHP protein level in the H-Zn group was lower than that in the control and the L-Zn group markedly. Our in vitro study indicated that the intestinal epithelial cells (IECs) absorbed nano-ZnO via endocytosis, and nano-Zn-induced TG deposition and lipogenesis were partially attributable to the endocytosis of nano-ZnO in IECs. Mechanistically, nano-ZnO-induced TG deposition was closely related to the metal responsive transcription factor 1 (MTF-1)-SHP pathway. Thus, for the first time, we found that the lipogenesis effects of nano-ZnO probably depended on the key gene shp, which is potentially regulated by MTF1 and/or FXR. This novel signaling pathway of MTF-1 through SHP may be relevant to explain the toxic effects and lipotoxicity ascribed to dietary nano-ZnO addition. |
format | Online Article Text |
id | pubmed-8584588 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85845882021-11-12 Dietary Nano-ZnO Is Absorbed via Endocytosis and ZIP Pathways, Upregulates Lipogenesis, and Induces Lipotoxicity in the Intestine of Yellow Catfish Chen, Shu-Wei Lv, Wu-Hong Wu, Kun Chen, Guang-Hui Chen, Fang Song, Chang-Chun Luo, Zhi Int J Mol Sci Article Nano-sized zinc oxide (nano-ZnO) affects lipid deposition, but its absorption patterns and mechanisms affecting lipid metabolism are still unclear. This study was undertaken to investigate the molecular mechanism of nano-ZnO absorption and its effects on lipid metabolism in the intestinal tissues of a widely distributed freshwater teleost yellow catfish Pelteobagrus fulvidraco. We found that 100 mg/kg dietary nano-ZnO (H-Zn group) significantly increased intestinal Zn contents. The zip6 and zip10 mRNA expression levels were higher in the H-Zn group than those in the control (0 mg/kg nano-ZnO), and zip4 mRNA abundances were higher in the control than those in the L-Zn (50 mg/kg nano-ZnO) and H-Zn groups. Eps15, dynamin1, dynamin2, caveolin1, and caveolin2 mRNA expression levels tended to reduce with dietary nano-ZnO addition. Dietary nano-ZnO increased triglyceride (TG) content and the activities of the lipogenic enzymes glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), and isocitrate dehydrogenase (ICDH), upregulated the mRNA abundances of lipogenic genes 6pgd, fatty acid synthase (fas), and sterol regulatory element binding protein 1 (srebp1), and reduced the mRNA expression of farnesoid X receptor (fxr) and small heterodimer partner (shp). The SHP protein level in the H-Zn group was lower than that in the control and the L-Zn group markedly. Our in vitro study indicated that the intestinal epithelial cells (IECs) absorbed nano-ZnO via endocytosis, and nano-Zn-induced TG deposition and lipogenesis were partially attributable to the endocytosis of nano-ZnO in IECs. Mechanistically, nano-ZnO-induced TG deposition was closely related to the metal responsive transcription factor 1 (MTF-1)-SHP pathway. Thus, for the first time, we found that the lipogenesis effects of nano-ZnO probably depended on the key gene shp, which is potentially regulated by MTF1 and/or FXR. This novel signaling pathway of MTF-1 through SHP may be relevant to explain the toxic effects and lipotoxicity ascribed to dietary nano-ZnO addition. MDPI 2021-11-07 /pmc/articles/PMC8584588/ /pubmed/34769475 http://dx.doi.org/10.3390/ijms222112047 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Shu-Wei Lv, Wu-Hong Wu, Kun Chen, Guang-Hui Chen, Fang Song, Chang-Chun Luo, Zhi Dietary Nano-ZnO Is Absorbed via Endocytosis and ZIP Pathways, Upregulates Lipogenesis, and Induces Lipotoxicity in the Intestine of Yellow Catfish |
title | Dietary Nano-ZnO Is Absorbed via Endocytosis and ZIP Pathways, Upregulates Lipogenesis, and Induces Lipotoxicity in the Intestine of Yellow Catfish |
title_full | Dietary Nano-ZnO Is Absorbed via Endocytosis and ZIP Pathways, Upregulates Lipogenesis, and Induces Lipotoxicity in the Intestine of Yellow Catfish |
title_fullStr | Dietary Nano-ZnO Is Absorbed via Endocytosis and ZIP Pathways, Upregulates Lipogenesis, and Induces Lipotoxicity in the Intestine of Yellow Catfish |
title_full_unstemmed | Dietary Nano-ZnO Is Absorbed via Endocytosis and ZIP Pathways, Upregulates Lipogenesis, and Induces Lipotoxicity in the Intestine of Yellow Catfish |
title_short | Dietary Nano-ZnO Is Absorbed via Endocytosis and ZIP Pathways, Upregulates Lipogenesis, and Induces Lipotoxicity in the Intestine of Yellow Catfish |
title_sort | dietary nano-zno is absorbed via endocytosis and zip pathways, upregulates lipogenesis, and induces lipotoxicity in the intestine of yellow catfish |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584588/ https://www.ncbi.nlm.nih.gov/pubmed/34769475 http://dx.doi.org/10.3390/ijms222112047 |
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