Role of AMP-activated protein kinase in sepsis-induced cardiovascular dysfunction

Angé, Marine; Castanares-Zapatero, Diego; Bertrand, Luc; Horman, Sandrine; Beauloye, Christophe

doi:10.1152/ajpheart.00015.2019

Cited by 2 publications

(3 citation statements)

References 7 publications

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“…Previously, strategies to inhibit FASN and activate AMPK have been demonstrated to have beneficial effects in experimental models of sepsis and endotoxaemia. 21,26,41 In our study, none of the strategies was able to ameliorate LPS-induced cardiac dysfunction,…”

Section: Discussioncontrasting

confidence: 55%

“…Previously, strategies to inhibit FASN and activate AMPK have been demonstrated to have beneficial effects in experimental models of sepsis and endotoxaemia 21,26,41 . In our study, none of the strategies was able to ameliorate LPS‐induced cardiac dysfunction, although, in the case of FASN inhibition, mitochondrial FAO and overall cardiac fatty acid metabolism were substantially improved.…”

Section: Discussionmentioning

confidence: 50%

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Inhibition of CPT2 exacerbates cardiac dysfunction and inflammation in experimental endotoxaemia

Makrecka-Kūka

Korzh

Videja

et al. 2020

J Cellular Molecular Medi

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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.

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