Abstract：
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.
摘要：
脂质代谢紊乱是几种严重影响公众健康的慢性代谢性疾病的主要原因。Salusin-α,血管活性肽,已被证明可以减轻脂质代谢紊乱，尽管其作用机制尚未报道。为了研究Salusin-α对脂质代谢的影响和潜在机制，使用慢病毒载体过表达或敲低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染色并通过测量几种生化指标来评估脂质积累的程度。随后，生物信息学用于分析可能参与脂质代谢紊乱的信号通路。最后,半定量PCR和免疫印迹用于验证肝激酶B1（LKB1）/AMPK通路的参与。化合物C,AMPK的抑制剂,被用来进一步证实这种机制的参与。结果表明，Salusin-α显着减弱脂质积累，炎症和氧化应激。此外,Salusin-α增加了LKB1和AMPK的水平，抑制固醇调节元件结合蛋白-1c的表达，脂肪酸合成酶和乙酰辅酶A羧化酶。化合物C的添加消除了Salusin-α介导的AMPK对下游信号分子的调节。总之,Salusin-α的过表达激活了LKB1/AMPK途径，这反过来又抑制了HepG2细胞中的脂质积累。这提供了对Salusin‑α改善脂质代谢紊乱的潜在机制的见解，同时确定了潜在的治疗靶标。
