Conclusions
Collectively, our study suggested that fructose aggravated CuD-induced cardiac remodeling through the blockade of autophagic flux via SERCA2a decreasing-induced Ca2+ imbalance.
Methods
We established a model of CuD- or fructose-induced cardiac hypertrophy in 3-week-old male Sprague-Dawley (SD) rats by CuD diet supplemented with or without 30% fructose for 4 weeks. In vitro study was performed by treating cardiomyocytes with tetrathiomolydbate (TM) and fructose. Echocardiography, histology analysis, immunofluorescence, western blotting, and qPCR were performed. Key findings: Our findings revealed that CuD caused noticeable cardiac hypertrophy either in the presence or absence of fructose supplement. Fructose exacerbated CuD-induced cardiac remodeling and intramyocardial lipid accumulation. Furthermore, we presented that the inhibition of autophagic flux caused by Ca2+ disturbance is the key mechanism by which CuD- or fructose-induced cardiac remodeling. The reduced expression of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) in cardiomyocytes accounts for the elevated cytoplasmic Ca2+ concentration. Conclusions: Collectively, our study suggested that fructose aggravated CuD-induced cardiac remodeling through the blockade of autophagic flux via SERCA2a decreasing-induced Ca2+ imbalance.