AMP Activated Protein Kinase Is Indispensable for Myocardial Adaptation to Caloric Restriction in Mice

Kai Chen, Satoru Kobayashi, Xianmin Xu, Benoit Viollet, Qiangrong Liang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Caloric restriction (CR) is a robust dietary intervention known to enhance cardiovascular health. AMP activated protein kinase (AMPK) has been suggested to mediate the cardioprotective effects of CR. However, this hypothesis remains to be tested by using definitive loss-of-function animal models. In the present study, we subjected AMPKα2 knockout (KO) mice and their wild type (WT) littermates to a CR regimen that reduces caloric intake by 20%-40% for 4 weeks. CR decreased body weight, heart weight and serum levels of insulin in both WT and KO mice to the same degree, indicating the effectiveness of the CR protocol. CR activated cardiac AMPK signaling in WT mice, but not in AMPKα2 KO mice. Correspondingly, AMPKα2 KO mice had markedly reduced cardiac function during CR as determined by echocardiography and hemodynamic measurements. The compromised cardiac function was associated with increased markers of oxidative stress, endoplasmic reticulum stress and myocyte apoptosis. Mechanistically, CR down-regulated the expression of ATP5g2, a subunit of mitochondrial ATP synthase, and reduced ATP content in AMPKα2 KO hearts, but not in WT hearts. In addition, CR accelerated cardiac autophagic flux in WT mice, but failed to do so in AMPKα2 KO mice. These results demonstrated that without AMPK, CR triggers adverse effects that can lead to cardiac dysfunction, suggesting that AMPK signaling pathway is indispensible for energy homeostasis and myocardial adaptation to CR, a dietary intervention that normally produces beneficial cardiac effects.

Original languageEnglish (US)
Article numbere59682
JournalPLoS One
Volume8
Issue number3
DOIs
StatePublished - Mar 19 2013
Externally publishedYes

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AMP-activated protein kinase
Caloric Restriction
AMP-Activated Protein Kinases
mice
Knockout Mice
heart
cardiac output
cardioprotective effect
dietary restriction
H-transporting ATP synthase
echocardiography
hemodynamics
Mitochondrial Proton-Translocating ATPases
endoplasmic reticulum
myocytes
homeostasis
energy intake
Echocardiography
oxidative stress
insulin

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

AMP Activated Protein Kinase Is Indispensable for Myocardial Adaptation to Caloric Restriction in Mice. / Chen, Kai; Kobayashi, Satoru; Xu, Xianmin; Viollet, Benoit; Liang, Qiangrong.

In: PLoS One, Vol. 8, No. 3, e59682, 19.03.2013.

Research output: Contribution to journalArticle

Chen, Kai ; Kobayashi, Satoru ; Xu, Xianmin ; Viollet, Benoit ; Liang, Qiangrong. / AMP Activated Protein Kinase Is Indispensable for Myocardial Adaptation to Caloric Restriction in Mice. In: PLoS One. 2013 ; Vol. 8, No. 3.
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