Document Detail

Activity level, apoptosis, and development of cachexia in Apc(Min/+) mice.
MedLine Citation:
PMID:  20651218     Owner:  NLM     Status:  MEDLINE    
Criteria for diagnosing cachexia in adults include unintentional loss in body weight, decreased strength, fatigue, anorexia, and low muscle mass. Cachexia is also associated with systemic inflammation, altered metabolism, and anemia. The Apc(Min/+) mouse is a model of cachexia directly related to intestinal tumor burden and subsequent chronic inflammation. These mice also demonstrate muscle weakness, fatigue, decreased volitional activity, and elevated circulating IL-6 levels. The purpose of this study was to determine the time course of changes in physical activity and their relationship to anemia, muscle apoptosis, and muscle mass and body mass loss during cachexia. A subset of male Apc(Min/+) mice were given access to voluntary activity wheels from 5 to 26 wk of age, while sedentary male Apc(Min/+) mice were housed in cages lacking wheels. At the study's end mice were stratified by cachectic symptoms. Severely cachectic mice had decreased wheel running performance at 15 wk of age, while anemia and body weight loss were not present until 18 wk of age. Severely cachectic mice had lower hemoglobin levels compared with mildly cachectic mice at 13, 18, and 22 wk of age. Severely cachectic mice also demonstrated threefold more BCL2-associated X protein (BAX) protein in the gastrocnemius muscle at 26 wk of age compared with mildly cachectic mice. In sedentary Apc(Min/+) mice at 26 wk of age anemia was present, and markers of apoptosis were induced in severely cachectic muscle. Proapoptotic protein expression was induced in both red and white portions of gastrocnemius muscle as well as in soleus muscle of severely cachectic mice compared with mildly cachectic mice. These data demonstrate that decrements in wheel running performance precede loss of body mass and that inherent muscle oxidative capacity is not protective against muscle apoptosis.
Kristen A Baltgalvis; Franklin G Berger; Maria Marjorette O Peña; J Mark Davis; James P White; James A Carson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-07-22
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  109     ISSN:  1522-1601     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-13     Completed Date:  2011-05-23     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1155-61     Citation Subset:  IM    
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MeSH Terms
Adenomatous Polyposis Coli / genetics*,  metabolism,  pathology,  physiopathology
Anemia / blood,  genetics
Cachexia / genetics*,  metabolism,  pathology,  physiopathology
Disease Models, Animal
Gene Expression Regulation
Genes, APC*
Hemoglobins / metabolism
Mice, Inbred C57BL
Mice, Mutant Strains
Motor Activity*
Muscle, Skeletal / metabolism,  pathology*,  physiopathology*
Severity of Illness Index
Time Factors
Weight Loss
bcl-2-Associated X Protein / metabolism
Grant Support
1R01-CA-121249/CA/NCI NIH HHS; P20 RR-017698/RR/NCRR NIH HHS; R01 CA121249/CA/NCI NIH HHS
Reg. No./Substance:
0/Bax protein, mouse; 0/Hemoglobins; 0/bcl-2-Associated X Protein

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