Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice

Takahiro Fujimoto, Kyoko Miyasaka, Midori Koyanagi, Toshiyuki Tsunoda, Iwai Baba, Keiko Doi, Minoru Ohta, Norihiro Kato, Takehiko Sasazuki, Senji Shirasawa

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere4240
JournalPloS one
Volume4
Issue number1
DOIs
Publication statusPublished - Jan 21 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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