The suppression of energy metabolism is one of cornerstones of cardiac dysfunction in sepsis/endotoxaemia. To investigate the role of fatty acid oxidation (FAO) in the progression of inflammation‐induced cardiac dysfunction, we compared the effects of FAO‐targeting compounds on mitochondrial and cardiac function in an experimental model of lipopolysaccharide (LPS)‐induced endotoxaemia. In LPS‐treated mice, endotoxaemia‐induced inflammation significantly decreased cardiac FAO and increased pyruvate metabolism, while cardiac mechanical function was decreased. AMP‐activated protein kinase activation by A769662 improved mitochondrial FAO without affecting cardiac function and inflammation‐related gene expression during endotoxaemia. Fatty acid synthase inhibition by C75 restored both cardiac and mitochondrial FAO; however, no effects on inflammation‐related gene expression and cardiac function were observed. In addition, the inhibition of carnitine palmitoyltransferase 2 (CPT2)‐dependent FAO by aminocarnitine resulted in the accumulation of FAO intermediates, long‐chain acylcarnitines, in the heart. As a result, cardiac pyruvate metabolism was inhibited, which further exacerbated inflammation‐induced cardiac dysfunction. In conclusion, although inhibition of CPT2‐dependent FAO is detrimental to cardiac function during endotoxaemia, present findings show that the restoration of cardiac FAO alone is not sufficient to recover cardiac function. Rescue of cardiac FAO should be combined with anti‐inflammatory therapy to ameliorate cardiac dysfunction in endotoxaemia.

中文翻译：

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CPT2的抑制加剧了实验性内毒素血症的心脏功能障碍和炎症。

能量代谢的抑制是败血症/内毒素血症中心脏功能障碍的基石之一。为了研究脂肪酸氧化（FAO）在炎症引起的心脏功能障碍进展中的作用，我们在脂多糖（LPS）引起的内毒素血症实验模型中比较了针对FAO的化合物对线粒体和心脏功能的影响。在接受LPS处理的小鼠中，内毒素血症引起的炎症显着降低了心脏的FAO和丙酮酸的代谢，而心脏的机械功能却降低了。内毒素血症期间，A769662激活的AMP激活的蛋白激酶可改善线粒体FAO而不影响心脏功能和炎症相关基因的表达。C75抑制脂肪酸合酶可恢复心脏和线粒体的粮农组织；然而，没有观察到对炎症相关基因表达和心脏功能的影响。此外，氨基肉碱对肉碱棕榈酰转移酶2（CPT2）依赖性FAO的抑制导致心脏中FAO中间体长链酰基肉碱的积累。结果，心脏丙酮酸的代谢受到抑制，这进一步加剧了炎症引起的心脏功能障碍。总之，尽管抑制CPT2依赖性FAO对内毒素血症期间的心脏功能有害，但目前的发现表明，仅恢复心脏FAO不足以恢复心脏功能。心脏抢救FAO应与抗炎治疗相结合，以减轻内毒素血症中的心脏功能障碍。肉碱对肉碱棕榈酰转移酶2（CPT2）依赖性FAO的抑制作用导致心脏中的FAO中间体长链酰基肉碱积累。结果，心脏丙酮酸的代谢受到抑制，这进一步加剧了炎症引起的心脏功能障碍。总之，尽管抑制CPT2依赖性FAO对内毒素血症期间的心脏功能有害，但目前的发现表明，仅恢复心脏FAO不足以恢复心脏功能。心脏抢救FAO应与抗炎治疗相结合，以改善内毒素血症的心脏功能障碍。肉碱对肉碱棕榈酰转移酶2（CPT2）依赖性FAO的抑制作用导致心脏中的FAO中间体长链酰基肉碱积累。结果，心脏丙酮酸的代谢受到抑制，这进一步加剧了炎症引起的心脏功能障碍。总之，尽管抑制CPT2依赖的FAO对内毒素血症期间的心脏功能有害，但目前的发现表明，仅恢复心脏FAO不足以恢复心脏功能。心脏抢救FAO应与抗炎治疗相结合，以减轻内毒素血症中的心脏功能障碍。这进一步加剧了炎症引起的心脏功能障碍。总之，尽管抑制CPT2依赖性FAO对内毒素血症期间的心脏功能有害，但目前的发现表明，仅恢复心脏FAO不足以恢复心脏功能。心脏抢救FAO应与抗炎治疗相结合，以减轻内毒素血症中的心脏功能障碍。这进一步加剧了炎症引起的心脏功能障碍。总之，尽管抑制CPT2依赖的FAO对内毒素血症期间的心脏功能有害，但目前的发现表明，仅恢复心脏FAO不足以恢复心脏功能。心脏抢救FAO应与抗炎治疗相结合，以减轻内毒素血症中的心脏功能障碍。