Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, China.
School of Medical Technology, Anhui Medical College, Hefei 230601, Anhui, China.
Biomed Environ Sci. 2024 Aug 20;37(8):850-864. doi: 10.3967/bes2024.081.
Microcystin-leucine-arginine (MC-LR) exposure induces lipid metabolism disorders in the liver. Secreted frizzled-related protein 5 (SFRP5) is a natural antagonist of winglesstype MMTV integration site family, member 5A (Wnt5a) and an anti-inflammatory adipocytokine. In this study, we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5, which has anti-inflammatory effects, can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase (JNK) pathway.
We exposed mice to MC-LR to induce liver lipid metabolism disorders. Subsequently, mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR, and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed.
MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner. SFRP5 overexpression in AML12 cells suppressed MC-LR-induced inflammation. Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK.
MC-LR can induce lipid metabolism disorders in mice, and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.
微囊藻毒素-亮氨酸-精氨酸（MC-LR）暴露会导致肝脏脂质代谢紊乱。分泌卷曲相关蛋白 5（SFRP5）是 Wnt5a 的天然拮抗剂，也是一种抗炎脂肪细胞因子。本研究旨在探讨 MC-LR 是否会诱导肝细胞脂质代谢紊乱，以及具有抗炎作用的 SFRP5 是否可以通过抑制 Wnt5a/Jun N-末端激酶（JNK）通路来减轻肝脂质代谢的影响。
我们用 MC-LR 处理小鼠以诱导肝脂质代谢紊乱。随后，用 MC-LR 处理过表达 SFRP5 或未表达 SFRP5 的小鼠肝细胞，并观察 SFRP5 过表达对 MC-LR 诱导的炎症和 Wnt5a/JNK 激活的影响。
MC-LR 暴露会诱导小鼠肝脏脂质代谢紊乱，并呈浓度依赖性显著降低 SFRP5 mRNA 和蛋白水平。AML12 细胞中 SFRP5 的过表达抑制了 MC-LR 诱导的炎症。SFRP5 的过表达也抑制了 Wnt5a 和 JNK 的磷酸化。
MC-LR 可诱导小鼠发生脂质代谢紊乱，SFRP5 通过抑制 Wnt5a/JNK 信号通路可减轻小鼠肝脂质代谢紊乱。
