Optimization of cardiac metabolism in heart failure

Tomohisa Nagoshi, Michihiro Yoshimura, Giuseppe M C Rosano, Gary D. Lopaschuk, Seibu Mochizuki

Research output: Contribution to journalArticlepeer-review

Abstract

The derangement of the cardiac energy substrate metabolism plays a key role in the pathogenesis of heart failure. The utilization of non-carbohydrate substrates, such as fatty acids, is the predominant metabolic pathway in the normal heart, because this provides the highest energy yield per molecule of substrate metabolized. In contrast, glucose becomes an important preferential substrate for metabolism and ATP generation under specific pathological conditions, because it can provide greater efficiency in producing high energy products per oxygen consumed compared to fatty acids. Manipulations that shift energy substrate utilization away from fatty acids toward glucose can improve the cardiac function and slow the progression of heart failure. However, insulin resistance, which is highly prevalent in the heart failure population, impedes this adaptive metabolic shift. Therefore, the acceleration of the glucose metabolism, along with the restoration of insulin sensitivity, would be the ideal metabolic therapy for heart failure. This review discusses the therapeutic potential of modifying substrate utilization to optimize cardiac metabolism in heart failure.

Original languageEnglish
Pages (from-to)3846-3853
Number of pages8
JournalCurrent Pharmaceutical Design
Volume17
Issue number35
Publication statusPublished - Dec 2011

Keywords

  • Heart failure
  • Insulin resistance
  • Metabolic therapy
  • Myocardial glucose and fatty acid metabolism

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

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