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Scientific article
English

Differential effects of high-fat diet on myocardial lipid metabolism in failing and nonfailing hearts with angiotensin II-mediated cardiac remodeling in mice

Published inAmerican journal of physiology. Heart and circulatory physiology, vol. 302, no. 9, p. H1795-1805
Publication date2012
Abstract

Normal myocardium adapts to increase of nutritional fatty acid supply by upregulation of regulatory proteins of the fatty acid oxidation pathway. Because advanced heart failure is associated with reduction of regulatory proteins of fatty acid oxidation, we hypothesized that failing myocardium may not be able to adapt to increased fatty acid intake and therefore undergo lipid accumulation, potentially aggravating myocardial dysfunction. We determined the effect of high-fat diet in transgenic mice with overexpression of angiotensinogen in the myocardium (TG1306/R1). TG1306/R1 mice develop ANG II-mediated left ventricular hypertrophy, and at one year of age approximately half of the mice present heart failure associated with reduced expression of regulatory proteins of fatty acid oxidation and reduced palmitate oxidation during ex vivo working heart perfusion. Hypertrophied hearts from TG1306/R1 mice without heart failure adapted to high-fat feeding, similarly to hearts from wild-type mice, with upregulation of regulatory proteins of fatty acid oxidation and enhancement of palmitate oxidation. There was no myocardial lipid accumulation or contractile dysfunction. In contrast, hearts from TG1306/R1 mice presenting heart failure were unable to respond to high-fat feeding by upregulation of fatty acid oxidation proteins and enhancement of palmitate oxidation. This resulted in accumulation of triglycerides and ceramide in the myocardium, and aggravation of contractile dysfunction. In conclusion, hearts with ANG II-induced contractile failure have lost the ability to enhance fatty acid oxidation in response to increased fatty acid supply. The ensuing accumulation of lipid compounds may play a role in the observed aggravation of contractile dysfunction.

Keywords
  • Angiotensin II/metabolism
  • Angiotensinogen/genetics/metabolism
  • Animals
  • Diet, High-Fat
  • Dietary Fats/pharmacology
  • Fatty Acids/metabolism
  • Heart Failure/metabolism
  • Hypertrophy, Left Ventricular/metabolism/physiopathology
  • Lipid Metabolism/drug effects
  • Male
  • Mice
  • Mice, Transgenic
  • Models, Animal
  • Myocardial Contraction/drug effects
  • Myocardium/metabolism
  • Oxidation-Reduction
  • Palmitates/metabolism
  • Triglycerides/metabolism
  • Ventricular Remodeling/physiology
Funding
  • Swiss National Science Foundation - Plasticity of expression pattern of key regulatory proteins of glucose and fatty acid metabolism during myocyte remodeling.
  • Swiss National Science Foundation - 3100B0109212/1
Citation (ISO format)
PELLIEUX, Corinne et al. Differential effects of high-fat diet on myocardial lipid metabolism in failing and nonfailing hearts with angiotensin II-mediated cardiac remodeling in mice. In: American journal of physiology. Heart and circulatory physiology, 2012, vol. 302, n° 9, p. H1795–1805. doi: 10.1152/ajpheart.01023.2011
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Article (Published version)
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Identifiers
ISSN of the journal0363-6135
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