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Myocardial fatty acid uptake through CD36 is indispensable for sufficient bioenergetic metabolism to prevent progression of pressure overload-induced heart failure

The energy metabolism of the failing heart is characterized by reduced fatty acid (FA) oxidation and an increase in glucose utilization. However, little is known about how energy metabolism-function relationship is relevant to pathophysiology of heart failure. Recent study showed that the genetic de...

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Autores principales: Umbarawan, Yogi, Syamsunarno, Mas Rizky A. A., Koitabashi, Norimichi, Obinata, Hideru, Yamaguchi, Aiko, Hanaoka, Hirofumi, Hishiki, Takako, Hayakawa, Noriyo, Sano, Motoaki, Sunaga, Hiroaki, Matsui, Hiroki, Tsushima, Yoshito, Suematsu, Makoto, Kurabayashi, Masahiko, Iso, Tatsuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089997/
https://www.ncbi.nlm.nih.gov/pubmed/30104639
http://dx.doi.org/10.1038/s41598-018-30616-1
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author Umbarawan, Yogi
Syamsunarno, Mas Rizky A. A.
Koitabashi, Norimichi
Obinata, Hideru
Yamaguchi, Aiko
Hanaoka, Hirofumi
Hishiki, Takako
Hayakawa, Noriyo
Sano, Motoaki
Sunaga, Hiroaki
Matsui, Hiroki
Tsushima, Yoshito
Suematsu, Makoto
Kurabayashi, Masahiko
Iso, Tatsuya
author_facet Umbarawan, Yogi
Syamsunarno, Mas Rizky A. A.
Koitabashi, Norimichi
Obinata, Hideru
Yamaguchi, Aiko
Hanaoka, Hirofumi
Hishiki, Takako
Hayakawa, Noriyo
Sano, Motoaki
Sunaga, Hiroaki
Matsui, Hiroki
Tsushima, Yoshito
Suematsu, Makoto
Kurabayashi, Masahiko
Iso, Tatsuya
author_sort Umbarawan, Yogi
collection PubMed
description The energy metabolism of the failing heart is characterized by reduced fatty acid (FA) oxidation and an increase in glucose utilization. However, little is known about how energy metabolism-function relationship is relevant to pathophysiology of heart failure. Recent study showed that the genetic deletion of CD36 (CD36KO), which causes reduction in FA use with an increased reliance on glucose, accelerates the progression from compensated hypertrophy to heart failure. Here, we show the mechanisms by which CD36 deletion accelerates heart failure in response to pressure overload. CD36KO mice exhibited contractile dysfunction and death from heart failure with enhanced cardiac hypertrophy and interstitial fibrosis when they were subjected to transverse aortic constriction (TAC). The pool size in the TCA cycle and levels of high-energy phosphate were significantly reduced in CD36KO-TAC hearts despite an increase in glycolytic flux. De novo synthesis of non-essential amino acids was facilitated in CD36KO-TAC hearts, which could cause a further decline of the pool size. The ingestion of a diet enriched in medium-chain FA improved cardiac dysfunction in CD36KO-TAC hearts. These findings suggest that myocardial FA uptake through CD36 is indispensable for sufficient ATP production and for preventing an increased glycolytic flux-mediated structural remodeling during pressure overload-induced hypertrophy.
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spelling pubmed-60899972018-08-17 Myocardial fatty acid uptake through CD36 is indispensable for sufficient bioenergetic metabolism to prevent progression of pressure overload-induced heart failure Umbarawan, Yogi Syamsunarno, Mas Rizky A. A. Koitabashi, Norimichi Obinata, Hideru Yamaguchi, Aiko Hanaoka, Hirofumi Hishiki, Takako Hayakawa, Noriyo Sano, Motoaki Sunaga, Hiroaki Matsui, Hiroki Tsushima, Yoshito Suematsu, Makoto Kurabayashi, Masahiko Iso, Tatsuya Sci Rep Article The energy metabolism of the failing heart is characterized by reduced fatty acid (FA) oxidation and an increase in glucose utilization. However, little is known about how energy metabolism-function relationship is relevant to pathophysiology of heart failure. Recent study showed that the genetic deletion of CD36 (CD36KO), which causes reduction in FA use with an increased reliance on glucose, accelerates the progression from compensated hypertrophy to heart failure. Here, we show the mechanisms by which CD36 deletion accelerates heart failure in response to pressure overload. CD36KO mice exhibited contractile dysfunction and death from heart failure with enhanced cardiac hypertrophy and interstitial fibrosis when they were subjected to transverse aortic constriction (TAC). The pool size in the TCA cycle and levels of high-energy phosphate were significantly reduced in CD36KO-TAC hearts despite an increase in glycolytic flux. De novo synthesis of non-essential amino acids was facilitated in CD36KO-TAC hearts, which could cause a further decline of the pool size. The ingestion of a diet enriched in medium-chain FA improved cardiac dysfunction in CD36KO-TAC hearts. These findings suggest that myocardial FA uptake through CD36 is indispensable for sufficient ATP production and for preventing an increased glycolytic flux-mediated structural remodeling during pressure overload-induced hypertrophy. Nature Publishing Group UK 2018-08-13 /pmc/articles/PMC6089997/ /pubmed/30104639 http://dx.doi.org/10.1038/s41598-018-30616-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Umbarawan, Yogi
Syamsunarno, Mas Rizky A. A.
Koitabashi, Norimichi
Obinata, Hideru
Yamaguchi, Aiko
Hanaoka, Hirofumi
Hishiki, Takako
Hayakawa, Noriyo
Sano, Motoaki
Sunaga, Hiroaki
Matsui, Hiroki
Tsushima, Yoshito
Suematsu, Makoto
Kurabayashi, Masahiko
Iso, Tatsuya
Myocardial fatty acid uptake through CD36 is indispensable for sufficient bioenergetic metabolism to prevent progression of pressure overload-induced heart failure
title Myocardial fatty acid uptake through CD36 is indispensable for sufficient bioenergetic metabolism to prevent progression of pressure overload-induced heart failure
title_full Myocardial fatty acid uptake through CD36 is indispensable for sufficient bioenergetic metabolism to prevent progression of pressure overload-induced heart failure
title_fullStr Myocardial fatty acid uptake through CD36 is indispensable for sufficient bioenergetic metabolism to prevent progression of pressure overload-induced heart failure
title_full_unstemmed Myocardial fatty acid uptake through CD36 is indispensable for sufficient bioenergetic metabolism to prevent progression of pressure overload-induced heart failure
title_short Myocardial fatty acid uptake through CD36 is indispensable for sufficient bioenergetic metabolism to prevent progression of pressure overload-induced heart failure
title_sort myocardial fatty acid uptake through cd36 is indispensable for sufficient bioenergetic metabolism to prevent progression of pressure overload-induced heart failure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089997/
https://www.ncbi.nlm.nih.gov/pubmed/30104639
http://dx.doi.org/10.1038/s41598-018-30616-1
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