Altered Energy Homeostasis and Resistance to Diet-induced Obesity in KRAP-deficient Mice

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2009 Jan 22

PMID 19156225

Citations 12

Authors

Takahiro Fujimoto

Kyoko Miyasaka

Midori Koyanagi

Toshiyuki Tsunoda

Iwai Baba

Keiko Doi

Minoru Ohta

Norihiro Kato

Takehiko Sasazuki

Senji Shirasawa

Affiliations

Soon will be listed here.

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.

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