Metabolic Remodeling And Its Correlative Mechanisms In Failing Heart

Background and ObjectivesIt is far important to keep energy metabolism balance in maintaining cardiac function. Recently it is proposed the notion of metabolic remodeling that metabolic disorder on myocardial substrate such as carbohydrate and lipid can alter the pathway of energy metabolism, which lead to myocardial structure and function impaired. Many a time, chronic cardiac failure associates with metabolic remodeling and presents affinity in between. Studying myocardial energy metabolism, especially metabolic remodeling in chronic congestive heart failure (CHF) possesses all-important significance. Excessive release of catecholamines during heart failure can act cytotoxic effect directly, increase lipolysis mediated by beta adrenoreceptors, lead to energy expenditure increased and fat stores decreased. It has been demonstrated that the hypertrophied and failing heart is characterized by a marked shift in substrate preference away from fatty acids towards glucose and reduction in the expression and activity of the peroxisome proliferator-activated receptor alpha and its target genes involved in fatty acid oxidation. Excess myocardial lipid accumulation due to an imbalance between fatty acid import and utilization, referred to as lipotoxicity, inhibits glycometabolism, and the consequent reduction of ATP production and exacerbation of cardiac energy metabolism. It was the theoretical fundamental of ameliorating metabolic remodeling and improving CHF to inhibit sympathetic nerve excess activation and reverse the cardiac metabolism substrate conversion.Beta3 adrenoceptors are upregulated in failing heart and these receptors are responsible for the unexpected negative inotropic effects of catecholamines and may be involved in pathophysiological mechanisms leading to heart failure. Stimulated by catecholamines, beta3 adrenoceptor can impact heart metabolism through increasing lipodieresis. A novel signaling pathway for mediation of beta3 adrenergic activation of the mitogen-activated protein kinases Erk1/2 has recently been proposed. PPARαactivity is...