Pan Jintong, Ye Wei, Zhang Jinmeng, Fan Ye, Chen Zaohong, Wang Yuxue, Liu Xiang
Department of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei, China.
Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Liver Int. 2025 Sep;45(9):e70252. doi: 10.1111/liv.70252.
Non-alcoholic fatty liver disease is now a significant public health issue globally. Salusin-β, a vasoactive peptide, plays a role in lipid metabolism regulation, but its mechanism remains unreported.
We studied the effects of Salusin-β on lipid metabolism and its mechanism by creating a NAFLD model in C57BL/6J mice and inducing steatosis in HepG2 cells. Then, shSalusin-β lentivirus was applied to transfect into the animals and cells, and the degree of lipid accumulation was assessed by staining and various biochemical indexes. Subsequently, Semi-Quantitative PCR, Western Blot, molecular docking, and Co-Immunoprecipitation were utilised to probe the downstream target FTO and then to verify the protein and mRNA changes of liposynthesis and catabolism genes downstream of FTO. Overexpressed FTO lentivirus was further employed to confirm this mechanism.
The results showed that knockdown of Salusin-β significantly attenuated the degree of lipid accumulation in mice and cells. In addition, shSalusin-β inhibited the expression of FTO, thereby inhibiting the expression of downstream sterol regulatory element binding protein-1c, fatty acid synthase, and promoting the expression of peroxisome proliferators-activated receptors α and carnitine palmitoyl transferase 1. Transfection of overexpressed FTO then eliminated the regulatory effect of shSalusin-β on downstream molecules.
In conclusion, knockdown of Salusin-β reduced FTO production, thereby alleviating lipid metabolism disorders. This provides a potential mechanism for elucidating the reduction of lipid metabolism by knockdown of Salusin-β and a potential target for the treatment of NAFLD.
非酒精性脂肪性肝病目前是全球一个重要的公共卫生问题。Salusin-β是一种血管活性肽，在脂质代谢调节中发挥作用，但其机制尚未见报道。
我们通过在C57BL/6J小鼠中建立非酒精性脂肪性肝病模型并在HepG2细胞中诱导脂肪变性，研究了Salusin-β对脂质代谢的影响及其机制。然后，应用shSalusin-β慢病毒转染动物和细胞，通过染色和各种生化指标评估脂质积累程度。随后，利用半定量PCR、蛋白质印迹、分子对接和免疫共沉淀技术探究下游靶点FTO，进而验证FTO下游脂肪合成和分解代谢基因的蛋白质和mRNA变化。进一步使用过表达FTO慢病毒来证实这一机制。
结果显示，敲低Salusin-β可显著减轻小鼠和细胞中的脂质积累程度。此外，shSalusin-β抑制FTO表达，从而抑制下游固醇调节元件结合蛋白-1c、脂肪酸合酶的表达，并促进过氧化物酶体增殖物激活受体α和肉碱棕榈酰转移酶1的表达。转染过表达FTO后消除了shSalusin-β对下游分子的调节作用。
总之,敲低Salusin-β可减少FTO生成，从而减轻脂质代谢紊乱。这为阐明敲低Salusin-β减轻脂质代谢的潜在机制提供了依据，并为非酒精性脂肪性肝病的治疗提供了一个潜在靶点。
