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SHRs exhibited significantly intensified myocardial de novo pathway of CER synthesis as well as DAG accumulation compared to the control Wistar Kyoto rats. Besides, intramyocardial level of potentially cardioprotective sphingolipid, i.e., sphingosine-1-phosphate was considerably decreased in SHRs, whereas URB597 treatment restored the level of this derivative. Unexpectedly, ECS upregulation protected overloaded cardiac muscle against CER and DAG accumulation. Moreover, chronic URB597 treatment improved intramyocardial insulin signaling p
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