Li Kuanhang, Zhou Zhengzheng, Cao Yi
Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China.
NMPA Key Laboratory for Safety Evaluation of Cosmetics, Department of Hygiene Inspection & Quarantine Science, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China.
Ecotoxicol Environ Saf. 2025 Jan 15;290:117580. doi: 10.1016/j.ecoenv.2024.117580. Epub 2024 Dec 20.
Recently we proposed the possibility of orally exposed nanoparticles (NPs) to alter metabolite homeostasis by changing metabolism pathways, in addition to intestinal damages, but relatively few studies investigated the changes of metabolite profiles in multi-organs. This study investigated the influences of orally exposed SiO NPs on lipid profiles in gut-liver axis. To this end, we treated mice with 16, 160 or 1600 mg/kg bodyweight SiO NPs via intragastric route. After 5 days exposure (once a day), we observed that SiO NPs induced minimal pathological changes but increased most of the trace elements. Furthermore, lipid staining was gradually decreased in intestines and livers with the increase of NP levels. Consistently, lipidomics results showed that most of the lipid classes in mouse intestines and livers were decreased following SiO NP administration. We further identified the lipid classes significantly decreased in both intestines and livers, such as phosphatidylserine (PS), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE). Only a few lipid classes, such as anandamide, showed opposite trends in these organs. For metabolism pathway, SiO NPs suppressed autophagy, showing as a significant decrease of microtubule-associated protein 1 A/1B light chain 3 (LC3) and adipose triglyceride lipase (Atgl), accompanying with an accumulation of P62, in both intestines and livers. However, lysosomal-associated membrane protein 2 (Lamp2) showed different trend, that it was significantly increased in intestines but decreased in livers. Combined, our results indicated that intragastric administration of SiO NPs altered trace element balance and lipid profiles, accompanying with a change of autophagic lipolysis proteins, in mouse gut-liver axis.
最近我们提出，口服纳米颗粒（NPs）除了会造成肠道损伤外，还可能通过改变代谢途径来改变代谢物稳态，但相对较少的研究调查了多器官中代谢物谱的变化。本研究调查了口服二氧化硅纳米颗粒（SiO NPs）对肠-肝轴脂质谱的影响。为此，我们通过灌胃途径给小鼠施用16、160或1600毫克/千克体重的SiO NPs。暴露5天后（每天一次），我们观察到SiO NPs引起的病理变化极小，但大多数微量元素增加。此外，随着纳米颗粒水平的增加，肠道和肝脏中的脂质染色逐渐减少。一致地，脂质组学结果表明，施用SiO NPs后，小鼠肠道和肝脏中的大多数脂质类别减少。我们进一步确定了在肠道和肝脏中均显著减少的脂质类别，如磷脂酰丝氨酸（PS）、磷脂酰甘油（PG）和磷脂酰乙醇胺（PE）。只有少数脂质类别，如花生四烯乙醇胺，在这些器官中呈现相反的趋势。对于代谢途径，SiO NPs抑制自噬，表现为肠道和肝脏中微管相关蛋白1A/1B轻链3（LC3）和脂肪甘油三酯脂肪酶（Atgl）显著减少，同时伴有P62的积累。然而，溶酶体相关膜蛋白2（Lamp2）呈现不同趋势，它在肠道中显著增加，但在肝脏中减少。综合来看，我们的结果表明，灌胃施用SiO NPs会改变小鼠肠-肝轴中的微量元素平衡和脂质谱，并伴有自噬性脂肪分解蛋白的变化。
