Pyruvate dehydrogenase as a therapeutic target for obesity cardiomyopathy

Expert Opin Ther Targets. 2016 Jun;20(6):755-66. doi: 10.1517/14728222.2016.1126248. Epub 2016 Jan 8.

Abstract

Introduction: Obesity cardiomyopathy is a major public health problem with few specific therapeutic options. Abnormal cardiac substrate metabolism with reduced pyruvate dehydrogenase (PDH) activity is associated with energetic and functional cardiac impairment and may be a therapeutic target.

Areas covered: This review summarizes the changes to cardiac substrate and high energy phosphorus metabolism that occur in obesity and describes the links between abnormal metabolism and impairment of cardiac function. The available evidence for the currently available pharmacological options for selective metabolic therapy in obesity cardiomyopathy is reviewed.

Expert opinion: Pharmacological restoration of PDH activity is in general associated with favourable effects upon cardiac substrate metabolism and function in both animal models and small scale human studies, supporting a potential role as a therapeutic target.

Keywords: Obesity; heart failure; imaging; metabolism.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiomyopathies / drug therapy*
  • Cardiomyopathies / etiology
  • Disease Models, Animal
  • Energy Metabolism / physiology
  • Humans
  • Molecular Targeted Therapy
  • Obesity / complications
  • Obesity / drug therapy*
  • Phosphorus / metabolism
  • Pyruvate Dehydrogenase Complex / metabolism*

Substances

  • Pyruvate Dehydrogenase Complex
  • Phosphorus