PUBLICATION
Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism
- Authors
- Lou, B., Wu, H., Ott, H., Bennewitz, K., Wang, C., Poschet, G., Liu, H., Yuan, Z., Kroll, J., She, J.
- ID
- ZDB-PUB-230318-36
- Date
- 2023
- Source
- Journal of translational medicine 21: 199199 (Journal)
- Registered Authors
- Kroll, Jens
- Keywords
- Fatty acid, Heart failure, Sterol regulatory element binding proteins 1, Uric acid
- MeSH Terms
-
- Animals
- Fatty Acid Synthases/metabolism
- Fatty Acids/metabolism
- Heart Diseases*
- Heart Failure*/complications
- Humans
- Uric Acid
- Zebrafish/metabolism
- PubMed
- 36927819 Full text @ J Transl Med
Citation
Lou, B., Wu, H., Ott, H., Bennewitz, K., Wang, C., Poschet, G., Liu, H., Yuan, Z., Kroll, J., She, J. (2023) Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism. Journal of translational medicine. 21:199199.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping