College of Animal Sciences, Dairy Science Institute, MOE Key Laboratory of Molecular Animal Nutrition, Zhejiang University, Hangzhou, 310029, PR China.
Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310029, PR China.
Nat Commun. 2023 Jun 20;14(1):3643. doi: 10.1038/s41467-023-39423-3.
Accumulation of inorganic nanoparticles in living organisms can cause an increase in cellular reactive oxygen species (ROS) in a dose-dependent manner. Low doses of nanoparticles have shown possibilities to induce moderate ROS increases and lead to adaptive responses of biological systems, but beneficial effects of such responses on metabolic health remain elusive. Here, we report that repeated oral administrations of various inorganic nanoparticles, including TiO, Au, and NaYF nanoparticles at low doses, can promote lipid degradation and alleviate steatosis in the liver of male mice. We show that low-level uptake of nanoparticles evokes an unusual antioxidant response in hepatocytes by promoting Ces2h expression and consequently enhancing ester hydrolysis. This process can be implemented to treat specific hepatic metabolic disorders, such as fatty liver in both genetic and high-fat-diet obese mice without causing observed adverse effects. Our results demonstrate that low-dose nanoparticle administration may serve as a promising treatment for metabolic regulation.
无机纳米粒子在生物体内的积累会导致细胞内活性氧（ROS）的产生呈剂量依赖性增加。低剂量的纳米粒子已经显示出诱导适度 ROS 增加的可能性，并导致生物系统的适应性反应，但这种反应对代谢健康的有益影响仍不清楚。在这里，我们报告说，重复口服给予各种无机纳米粒子，包括 TiO2、Au 和 NaYF 纳米粒子，低剂量可以促进雄性小鼠肝脏的脂质降解和脂肪变性的缓解。我们表明，纳米粒子的低水平摄取通过促进 Ces2h 表达从而增强酯水解，在肝细胞中引发一种不寻常的抗氧化反应。这个过程可以用来治疗特定的肝脏代谢紊乱，如遗传和高脂肪饮食肥胖小鼠的脂肪肝，而不会产生观察到的不良反应。我们的结果表明，低剂量纳米粒子给药可能是一种有前途的代谢调节治疗方法。
