School of Medicine, Shanghai University, Shanghai, China.
Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China.
J Sep Sci. 2023 Dec;46(24):e2300452. doi: 10.1002/jssc.202300452. Epub 2023 Oct 25.
Few studies have examined the relationship between lipid metabolism and kidney stone formation, particularly the role of key lipid regulatory factors in kidney stone formation. We evaluated the effect of the lipid regulatory factor-peroxisome proliferator-activated receptor alpha on the formation of renal stones in mice by injecting them with glyoxylate followed by treatment with either a peroxisome proliferator-activated receptor alpha agonist fenofibrate or an antagonist GW6471 (GW). Liquid chromatography coupled with trapped ion mobility spectrometry-quadrupole-time-of-flight mass spectrometry-based lipidomics was used to determine the lipid profile in the mouse kidneys. Histological and biochemical analyses showed that the mice injected with glyoxylate exhibited crystal precipitation and renal dysfunction. Crystallization decreased significantly in the fenofibrate group, whereas it increased significantly in the GW group. A total of 184 lipids, including fatty acyls, glycerolipids, glycerophospholipids, and sphingolipids differed significantly between the mice in the model and control groups. Peroxisome proliferator-activated receptor alpha activity negatively correlated with glyoxylate-induced kidney stone formation in mice, which may be related to improved fatty acid oxidation, maintenance of ceramide/complex sphingolipids cycle balance, and alleviation of disorder in phospholipid metabolism.
很少有研究探讨脂质代谢与肾结石形成之间的关系，特别是关键脂质调节因子在肾结石形成中的作用。我们通过给小鼠注射乙醛酸，然后用过氧化物酶体增殖物激活受体α激动剂非诺贝特或拮抗剂 GW6471（GW）处理，评估脂质调节因子-过氧化物酶体增殖物激活受体α对小鼠肾结石形成的影响。采用液相色谱-串联离子淌度-四极杆飞行时间质谱脂质组学方法测定小鼠肾脏中的脂质谱。组织学和生化分析表明，注射乙醛酸的小鼠表现出晶体沉淀和肾功能障碍。在非诺贝特组中结晶明显减少，而在 GW 组中结晶明显增加。模型组和对照组小鼠之间共有 184 种脂质，包括脂肪酸、甘油酯、甘油磷脂和鞘脂，差异有统计学意义。过氧化物酶体增殖物激活受体α的活性与乙醛酸诱导的小鼠肾结石形成呈负相关，这可能与改善脂肪酸氧化、维持神经酰胺/复杂鞘脂循环平衡以及缓解磷脂代谢紊乱有关。
