AUTHOR=Wang Qingpeng , Chi Jiangyang , Wang Chen , Yuan Yanhong , Tian Rui , Yang Yun , Chen Xinzhong 

TITLE=CTRP3 attenuates myocardial lipotoxicity via suppression of lipid accumulation, inflammation, apoptosis, and mitochondrial oxidative stress

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2025.1575929

DOI=10.3389/fcvm.2025.1575929

ISSN=2297-055X

ABSTRACT=Myocardial lipotoxicity, a pathophysiological condition characterized by cardiomyocyte damage resulting from dysregulated fatty acid metabolism, plays a pivotal role in cardiovascular disease progression. C1q/tumor necrosis factor-related protein-3 (CTRP3), a novel adipocytokine with pleiotropic metabolic regulatory properties, has recently been implicated in lipid homeostasis modulation. Nevertheless, its cardioprotective potential against myocardial lipotoxicity remains poorly understood.ObjectiveA comprehensive approach combining in vivo high-fat diet (HFD) murine models and in vitro palmitic acid-induced cardiomyocyte injury systems was employed.Methodsthis study used animal and cellular experiments to verify the function of CTRP3.ResultsHFD feeding induced significant lipid droplet deposition in cardiomyocytes, concomitant with enhanced inflammatory responses, elevated apoptotic activity, and exacerbated oxidative stress, ultimately leading to cardiac dysfunction. Both cardiac-specific CTRP3 overexpression and exogenous recombinant CTRP3 (rCTRP3) administration demonstrated remarkable cardioprotective effects, manifested through: (1) Significant attenuation of intramyocardial lipid accumulation (p < 0.05) (2) Suppression inflammatory pathways (3) Inhibition of mitochondrial-dependent apoptosis (4) Enhancement of antioxidant defense systems. These coordinated effects substantially ameliorated lipotoxic myocardial damage and improved cardiac functional parameters.ConclusionOur findings reveal that CTRP3 confers robust protection against myocardial lipotoxicity through multi-modal mechanisms involving lipid metabolism regulation, anti-inflammatory actions, apoptosis inhibition, and oxidative stress mitigation, highlighting its therapeutic potential for metabolic cardiomyopathy.