Related Experiment Video
Updated: Aug 6, 2025

Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism
Bowen Lou1,2,3, Haoyu Wu1,2, Hannes Ott3
1Cardiovascular Department, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Background:
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.
Methods And Results:
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.
Conclusions:
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.
More Related Videos
07:52A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
Published on: November 7, 2017
09:40Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle
Published on: January 19, 2017
Related Concept Videos
Heart Failure Drugs: Diuretics
Pathophysiology of Heart Failure
Heart Failure V: Medical Management
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
Heart Failure I: Introduction
Heart Failure II: Pathophysiology