Document Detail

Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis.
MedLine Citation:
PMID:  22258505     Owner:  NLM     Status:  MEDLINE    
Exercise has beneficial effects on human health, including protection against metabolic disorders such as diabetes. However, the cellular mechanisms underlying these effects are incompletely understood. The lysosomal degradation pathway, autophagy, is an intracellular recycling system that functions during basal conditions in organelle and protein quality control. During stress, increased levels of autophagy permit cells to adapt to changing nutritional and energy demands through protein catabolism. Moreover, in animal models, autophagy protects against diseases such as cancer, neurodegenerative disorders, infections, inflammatory diseases, ageing and insulin resistance. Here we show that acute exercise induces autophagy in skeletal and cardiac muscle of fed mice. To investigate the role of exercise-mediated autophagy in vivo, we generated mutant mice that show normal levels of basal autophagy but are deficient in stimulus (exercise- or starvation)-induced autophagy. These mice (termed BCL2 AAA mice) contain knock-in mutations in BCL2 phosphorylation sites (Thr69Ala, Ser70Ala and Ser84Ala) that prevent stimulus-induced disruption of the BCL2-beclin-1 complex and autophagy activation. BCL2 AAA mice show decreased endurance and altered glucose metabolism during acute exercise, as well as impaired chronic exercise-mediated protection against high-fat-diet-induced glucose intolerance. Thus, exercise induces autophagy, BCL2 is a crucial regulator of exercise- (and starvation)-induced autophagy in vivo, and autophagy induction may contribute to the beneficial metabolic effects of exercise.
Congcong He; Michael C Bassik; Viviana Moresi; Kai Sun; Yongjie Wei; Zhongju Zou; Zhenyi An; Joy Loh; Jill Fisher; Qihua Sun; Stanley Korsmeyer; Milton Packer; Herman I May; Joseph A Hill; Herbert W Virgin; Christopher Gilpin; Guanghua Xiao; Rhonda Bassel-Duby; Philipp E Scherer; Beth Levine
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-18
Journal Detail:
Title:  Nature     Volume:  481     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-27     Completed Date:  2012-03-02     Revised Date:  2014-07-02    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  511-5     Citation Subset:  IM    
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MeSH Terms
Adiponectin / blood
Apoptosis Regulatory Proteins / genetics,  metabolism
Autophagy / drug effects,  genetics,  physiology*
Cells, Cultured
Dietary Fats / adverse effects
Food Deprivation / physiology
Gene Knock-In Techniques
Glucose / metabolism*
Glucose Intolerance / chemically induced,  prevention & control
Glucose Tolerance Test
Homeostasis* / drug effects
Leptin / blood
Mice, Transgenic
Muscle, Skeletal / cytology,  drug effects,  metabolism*
Myocardium / cytology,  metabolism*
Phosphorylation / genetics
Physical Conditioning, Animal / physiology*
Physical Endurance / genetics,  physiology
Physical Exertion / genetics,  physiology
Protein Binding / genetics
Proto-Oncogene Proteins / genetics,  metabolism*
Proto-Oncogene Proteins c-bcl-2
Running / physiology
Grant Support
1P01 DK0887761/DK/NIDDK NIH HHS; P01 DK088761/DK/NIDDK NIH HHS; P30 CA142543/CA/NCI NIH HHS; R01 CA109618/CA/NCI NIH HHS; R01 CA109618/CA/NCI NIH HHS; R01 CA112023/CA/NCI NIH HHS; R01 CA112023/CA/NCI NIH HHS; R01 DK055758/DK/NIDDK NIH HHS; R0I AI084887/AI/NIAID NIH HHS; R0I HL080244/HL/NHLBI NIH HHS; R0I HL090842/HL/NHLBI NIH HHS; RC1 DK086629/DK/NIDDK NIH HHS; RCI DK086629/DK/NIDDK NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Adiponectin; 0/Apoptosis Regulatory Proteins; 0/Becn1 protein, mouse; 0/Dietary Fats; 0/Leptin; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 114100-40-2/Bcl2 protein, mouse; IY9XDZ35W2/Glucose
Comment In:
Nat Rev Mol Cell Biol. 2012 Mar;13(3):136   [PMID:  22293615 ]
Cell Metab. 2012 Mar 7;15(3):273-4   [PMID:  22405064 ]
Erratum In:
Nature. 2013 Nov 7:503(7474):146

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