%0 Journal Article %T Altered Energy Homeostasis and Resistance to Diet-Induced Obesity in KRAP-Deficient Mice %A Takahiro Fujimoto %A Kyoko Miyasaka %A Midori Koyanagi %A Toshiyuki Tsunoda %A Iwai Baba %A Keiko Doi %A Minoru Ohta %A Norihiro Kato %A Takehiko Sasazuki %A Senji Shirasawa %J PLOS ONE %D 2009 %I Public Library of Science (PLoS) %R 10.1371/journal.pone.0004240 %X 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. %U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0004240