PMID- 23527250
OWN - NLM
STAT- MEDLINE
DCOM- 20130917
LR  - 20240308
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 3
DP  - 2013
TI  - AMP activated protein kinase is indispensable for myocardial adaptation to 
      caloric restriction in mice.
PG  - e59682
LID - 10.1371/journal.pone.0059682 [doi]
LID - e59682
AB  - 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 AMPKalpha2 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 AMPKalpha2 KO mice. 
      Correspondingly, AMPKalpha2 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 AMPKalpha2 KO hearts, but not in WT hearts. In addition, 
      CR accelerated cardiac autophagic flux in WT mice, but failed to do so in AMPKalpha2 
      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.
FAU - Chen, Kai
AU  - Chen K
AD  - Cardiovascular Health Research Center, Sanford Research, University of South 
      Dakota, Sioux Falls, South Dakota, United States of America.
FAU - Kobayashi, Satoru
AU  - Kobayashi S
FAU - Xu, Xianmin
AU  - Xu X
FAU - Viollet, Benoit
AU  - Viollet B
FAU - Liang, Qiangrong
AU  - Liang Q
LA  - eng
GR  - P20 GM103455/GM/NIGMS NIH HHS/United States
GR  - P20 RR017662/RR/NCRR NIH HHS/United States
GR  - 8 P20 GM103455-10/GM/NIGMS NIH HHS/United States
GR  - 5P20RR017662-10/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130319
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Insulin)
RN  - 0 (Triglycerides)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics/*metabolism
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Blotting, Western
MH  - Body Weight
MH  - *Caloric Restriction
MH  - Endoplasmic Reticulum Stress/physiology
MH  - Heart/*growth & development
MH  - Heart Function Tests
MH  - Homeostasis/*physiology
MH  - In Situ Nick-End Labeling
MH  - Insulin/blood
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Myocardium/*metabolism
MH  - Organ Size
MH  - Oxidative Stress/physiology
MH  - Signal Transduction/*physiology
MH  - Triglycerides/blood
PMC - PMC3602170
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/03/26 06:00
MHDA- 2013/09/18 06:00
PMCR- 2013/03/19
CRDT- 2013/03/26 06:00
PHST- 2012/12/20 00:00 [received]
PHST- 2013/02/16 00:00 [accepted]
PHST- 2013/03/26 06:00 [entrez]
PHST- 2013/03/26 06:00 [pubmed]
PHST- 2013/09/18 06:00 [medline]
PHST- 2013/03/19 00:00 [pmc-release]
AID - PONE-D-12-40479 [pii]
AID - 10.1371/journal.pone.0059682 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(3):e59682. doi: 10.1371/journal.pone.0059682. Epub 2013 Mar 19.