增加的循环尿酸（UA）浓度可能会扰乱心衰患者的心脏功能，但具体机制尚不清楚。在这里，我们提出高尿酸血症引起甾体调节元件结合蛋白1（SREBP1），进而激活肝脏脂肪酸生物合成反应导致心脏功能障碍。心衰患者中观察到了增加的循环尿酸，并与心脏功能负相关。此外，尿酸也与基于代谢组学的心衰患者循环脂质剖面相关。利用人肝癌细胞（HepG2）和Tg（myl7：egfp）斑马鱼，我们证明了UA通过SREBP1信号通路调节脂肪酸合成酶（FASN），导致游离脂肪酸（FFA）积累和能量代谢受损，这可以通过SREBP1沉默来解救。在ISO处理的斑马鱼中，UA加重了心力衰竭，导致心血管腔大小增加，心跳减少，心包水肿和心脏长伸形变。我们的发现表明，UA-SREBP1-FASN信号加重了FFA积累期间的心脏功能障碍。确定这种机制可能有助于心力衰竭的治疗和预防。© 2023. 作者。

Increased circulating uric acid (UA) concentration may disrupt cardiac function in heart failure patients, but the specific mechanism remains unclear. Here, we postulate that hyperuremia induces sterol regulatory element binding protein 1 (SREBP1), which in turn activate hepatic fatty acid biosynthesis response, leading to cardiac dysfunction.Increased circulating uric acid was observed in heart failure patients and inversely correlated to cardiac function. Besides, uric acid correlated to circulating lipids profile based on metabolomics in heart failure patients. Using cultured human hepatoellular carcinomas (HepG2) and Tg(myl7:egfp) zebrafish, we demonstrated that UA regulated fatty acid synthase (FASN) via SREBP1 signaling pathway, leading to FFA accumulation and impaired energy metabolism, which could be rescued via SREBP1 knockdown. In ISO treated zebrafish, UA aggravated heart failure via increased cardiovascular cavity size, decreased heart beats, pericardial edema and long-stretched heart deformation.Our findings suggest that UA-SREBP1-FASN signaling exacerbates cardiac dysfunction during FFA accumulation. Identification of this mechanism may help in treatment and prevention of heart failure.© 2023. The Author(s).