Jintong Pan, Chao Yang, Aohong Xu, Huan Zhang, Ye Fan, Rong Zeng, Lin Chen, Xiang Liu, Yuxue Wang
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Subsequently, bioinformatics was used to analyze the signaling pathways that may have been involved in lipid metabolism disorders. Finally, semi‑quantitative PCR and western blotting were used to verify the involvement of the liver kinase B1 (LKB1)/AMPK pathway. Compound C, an inhibitor of AMPK, was used to confirm this mechanism's involvement further. The results showed that Salusin‑α significantly attenuated lipid accumulation, inflammation and oxidative stress. In addition, Salusin‑α increased the levels of LKB1 and AMPK, which inhibited the expression of sterol regulatory element binding protein‑1c, fatty acid synthase and acetyl‑CoA carboxylase. The addition of Compound C abrogated the Salusin‑α‑mediated regulation of AMPK on downstream signaling molecules. In summary, overexpression of Salusin‑α activated the LKB1/AMPK pathway, which in turn inhibited lipid accumulation in HepG2 cells. 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引用次数: 0
摘要
脂质代谢紊乱是导致多种慢性代谢性疾病的主要原因,严重影响公众健康。Salusin-α是一种血管活性肽,已被证明可减轻脂质代谢紊乱,但其作用机制尚未见报道。为了研究 Salusin-α 对脂质代谢的影响和潜在机制,我们使用慢病毒载体过表达或敲除 Salusin-α。慢病毒转染 HepG2 细胞后,游离脂肪酸(FFA)诱导肝细胞脂肪变性。使用油红 O 染色法和测量几种生化指标来评估脂质积累的程度。随后,生物信息学分析了可能与脂质代谢紊乱有关的信号通路。最后,利用半定量 PCR 和 Western 印迹技术验证了肝脏激酶 B1 (LKB1)/AMPK 通路的参与。化合物 C 是一种 AMPK 抑制剂,用于进一步证实这一机制的参与。结果表明,Salusin-α 能显著减少脂质积累、炎症和氧化应激。此外,Salusin-α 还能提高 LKB1 和 AMPK 的水平,抑制固醇调节元件结合蛋白-1c、脂肪酸合成酶和乙酰-CoA 羧化酶的表达。化合物 C 的添加削弱了 Salusin-α 介导的 AMPK 对下游信号分子的调节作用。总之,过量表达 Salusin-α 激活了 LKB1/AMPK 通路,进而抑制了 HepG2 细胞的脂质积累。这揭示了 Salusin-α 改善脂质代谢紊乱的潜在机制,同时也确定了一个潜在的治疗靶点。
Salusin‑α alleviates lipid metabolism disorders via regulation of the downstream lipogenesis genes through the LKB1/AMPK pathway.
Lipid metabolism disorders are a major cause of several chronic metabolic diseases which seriously affect public health. Salusin‑α, a vasoactive peptide, has been shown to attenuate lipid metabolism disorders, although its mechanism of action has not been reported. To investigate the effects and potential mechanisms of Salusin‑α on lipid metabolism, Salusin‑α was overexpressed or knocked down using lentiviral vectors. Hepatocyte steatosis was induced by free fatty acid (FFA) after lentiviral transfection into HepG2 cells. The degree of lipid accumulation was assessed using Oil Red O staining and by measuring several biochemical indices. Subsequently, bioinformatics was used to analyze the signaling pathways that may have been involved in lipid metabolism disorders. Finally, semi‑quantitative PCR and western blotting were used to verify the involvement of the liver kinase B1 (LKB1)/AMPK pathway. Compound C, an inhibitor of AMPK, was used to confirm this mechanism's involvement further. The results showed that Salusin‑α significantly attenuated lipid accumulation, inflammation and oxidative stress. In addition, Salusin‑α increased the levels of LKB1 and AMPK, which inhibited the expression of sterol regulatory element binding protein‑1c, fatty acid synthase and acetyl‑CoA carboxylase. The addition of Compound C abrogated the Salusin‑α‑mediated regulation of AMPK on downstream signaling molecules. In summary, overexpression of Salusin‑α activated the LKB1/AMPK pathway, which in turn inhibited lipid accumulation in HepG2 cells. This provides insights into the potential mechanism underlying the mechanism by which Salusin‑α ameliorates lipid metabolism disorders while identifying a potential therapeutic target.
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