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Abstract
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.
Highlights
We explored the absorption mechanism of nano-ZnO and its effect on lipid deposition and metabolism in the intestine, which mechanistically provided the insights for the evaluation of Zn nutrition in vertebrates
We found that high dietary nano-ZnO addition tended to increase the activities of 6-phosphogluconate dehydrogenase (6PGD), glucose 6-phosphate dehydrogenase (G6PD), and isocitrate dehydrogenase (ICDH) and upregulated the mRNA abundances of 6pgd, acca, srebp1, and fas. 6PGD, G6PD, ICDH, ACCA, fatty acid synthase (FAS), and SREBP1 are key enzymes and genes mediating the lipogenesis [22,32]
The nanoparticles were absorbed into intestinal epithelial cells via the endocytosis pathway, while Zn2+ released from nano-ZnO was absorpted by the ZIP system
Summary
Nanoparticles (NPs) are defined as small materials with at least one dimension in the. 1–100 nm range [1]. Among these NPs, nano-scaled zinc oxide or zinc oxide nanoparticles (nano-ZnO or ZnO NPs) have been used widely in the fields of feed additives, cosmetics, material science, biomedicine, optics, and electronics [1,2]. NPs has led to their distribution in the environment. The concentration of nano-ZnO was estimated to be 100 μg/L (water) and a few mg/kg (soil) in the UK environment [2]
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