Altered Energy Homeostasis and Resistance to Diet-Induced Obesity in KRAP-Deficient MiceReportar como inadecuado




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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.



Autor: Takahiro Fujimoto, Kyoko Miyasaka, Midori Koyanagi, Toshiyuki Tsunoda, Iwai Baba, Keiko Doi, Minoru Ohta, Norihiro Kato, Takehiko

Fuente: http://plos.srce.hr/



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