Cardiac hypertrophy is characterized by a shift in metabolic substrate utilization. Therefore, the regulation of ketone body uptake and metabolism may have beneficial effects on heart injuries that induce cardiac remodelling. In this study, we investigated whether icariside II (ICS II) protects against cardiac hypertrophy in mice and cardiomyocytes. To create cardiac hypertrophy animal and cell models, mice were subjected to transverse aortic constriction (TAC), and embryonic rat cardiomyocytes (H9C2) were stimulated with angiotensin II, a neurohumoral stressor. Both the in vivo and in vitro results suggest that ICS II treatment ameliorated pressure overload–induced cardiac hypertrophy and preserved heart function. In addition, apoptosis and oxidative stress were reduced in the presence of ICS II. Moreover, ICS II inhibited excess autophagy in TAC‐induced hearts and angiotensin II–stimulated cardiomyocytes. Mechanistically, we found that ICS II administration regulated SIRT3 expression in cardiac remodelling. SIRT3 activation increased ketone body transportation and utilization. Collectively, our data show that ICS II attenuated cardiac hypertrophy by modulating ketone body and fatty acid metabolism, and that this was likely due to the activation of the SIRT3‐AMPK pathway. ICS II treatment may provide a new therapeutic strategy for improving myocardial metabolism in cardiac hypertrophy and heart failure.

中文翻译：

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ICS II通过调节代谢重构而不是通过抑制自噬来预防心肌肥大

心脏肥大的特征在于代谢底物利用率的变化。因此，酮体摄取和代谢的调节可能对诱发心脏重塑的心脏损伤具有有益作用。在这项研究中，我们调查了icariside II（ICS II）是否能预防小鼠和心肌细胞的心肌肥大。为了创建心脏肥大动物和细胞模型，对小鼠进行横动脉主动脉收缩（TAC），并用神经体液应激源血管紧张素II刺激胚胎大鼠心肌细胞（H9C2）。体内和体外结果均表明，ICS II治疗可改善压力超负荷引起的心脏肥大并保留心脏功能。另外，在ICS II的存在下，细胞凋亡和氧化应激降低。此外，ICS II抑制TAC诱导的心脏和血管紧张素II刺激的心肌细胞过度自噬。从机理上讲，我们发现ICS II给药可调节心脏重塑中的SIRT3表达。SIRT3激活增加了酮体的运输和利用。总体而言，我们的数据表明，ICS II通过调节酮体和脂肪酸代谢来减轻心脏肥大，这很可能是由于SIRT3-AMPK途径的激活所致。ICS II治疗可能为改善心脏肥大和心力衰竭中的心肌代谢提供新的治疗策略。我们的数据显示ICS II通过调节酮体和脂肪酸代谢来减轻心脏肥大，这可能是由于SIRT3-AMPK途径的激活所致。ICS II治疗可能为改善心肌肥大和心力衰竭的心肌代谢提供新的治疗策略。我们的数据显示ICS II通过调节酮体和脂肪酸代谢来减轻心脏肥大，这可能是由于SIRT3-AMPK途径的激活所致。ICS II治疗可能为改善心脏肥大和心力衰竭中的心肌代谢提供新的治疗策略。