UNIGE document Scientific Article
previous document  unige:88467  next document
add to browser collection
Title

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

Authors
Pedrazzini, Thierry
Published in American Journal of Physiology. Heart and Circulatory Physiology. 2012, vol. 302, no. 9, p. H1795-805
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/metabolismAngiotensinogen/genetics/metabolismAnimalsDiet, High-FatDietary Fats/pharmacologyFatty Acids/metabolismHeart Failure/metabolismHypertrophy, Left Ventricular/metabolism/physiopathologyLipid Metabolism/drug effectsMaleMiceMice, TransgenicModels, AnimalMyocardial Contraction/drug effectsMyocardium/metabolismOxidation-ReductionPalmitates/metabolismTriglycerides/metabolismVentricular Remodeling/physiology
Identifiers
PMID: 22408021
Full text
Article (Published version) (614 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Projects FNS: 3200-067873
FNS: 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. H1795-805. https://archive-ouverte.unige.ch/unige:88467

43 hits

0 download

Update

Deposited on : 2016-10-28

Export document
Format :
Citation style :