Document Detail


Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice.
MedLine Citation:
PMID:  19156225     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Obesity and related metabolic disorders have become leading causes of adult morbidity and mortality. KRAP (Ki-ras-induced actin-interacting protein) is a cytoskeleton-associated protein and a ubiquitous protein among tissues, originally identified as a cancer-related molecule, however, its physiological roles remain unknown. Here we demonstrate that KRAP-deficient (KRAP(-/-)) mice show enhanced metabolic rate, decreased adiposity, improved glucose tolerance, hypoinsulinemia and hypoleptinemia. KRAP(-/-) mice are also protected against high-fat diet-induced obesity and insulin resistance despite of hyperphagia. Notably, glucose uptake in the brown adipose tissue (BAT) in KRAP(-/-) mice is enhanced in an insulin-independent manner, suggesting that BAT is involved in altered energy homeostasis in KRAP(-/-) mice, although UCP (Uncoupling protein) expressions are not altered. Of interest is the down-regulation of fatty acid metabolism-related molecules, including acetyl-CoA carboxylase (ACC)-1, ACC-2 and fatty acid synthase in the liver of KRAP(-/-) mice, which could in part account for the metabolic phenotype in KRAP(-/-) mice. Thus, KRAP is a novel regulator in whole-body energy homeostasis and may be a therapeutic target in obesity and related diseases.
Authors:
Takahiro Fujimoto; Kyoko Miyasaka; Midori Koyanagi; Toshiyuki Tsunoda; Iwai Baba; Keiko Doi; Minoru Ohta; Norihiro Kato; Takehiko Sasazuki; Senji Shirasawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-21
Journal Detail:
Title:  PloS one     Volume:  4     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2009  
Date Detail:
Created Date:  2009-01-21     Completed Date:  2009-05-15     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e4240     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Acetyl-CoA Carboxylase / metabolism
Adipose Tissue / metabolism
Adiposity / genetics
Animal Feed
Animals
Fatty Acid Synthetase Complex / metabolism
Glucose / metabolism
Homeostasis
Insulin / metabolism
Liver / metabolism
Membrane Proteins / metabolism
Mice
Mice, Transgenic
Microfilament Proteins / genetics,  physiology*
Models, Biological
Obesity / genetics*,  pathology
Chemical
Reg. No./Substance:
0/Insulin; 0/KRAP protein, mouse; 0/Membrane Proteins; 0/Microfilament Proteins; 50-99-7/Glucose; EC 6.-/Fatty Acid Synthetase Complex; EC 6.4.1.2/Acetyl-CoA Carboxylase
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