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

Fingerprint

Nutrition
actin
Actins
homeostasis
obesity
Homeostasis
Obesity
Diet
mice
energy
diet
Acetyl-CoA Carboxylase
Proteins
Brown Adipose Tissue
proteins
Tissue
acetyl-CoA carboxylase
brown adipose tissue
Insulin
Glucose

All Science Journal Classification (ASJC) codes

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

Cite this

Fujimoto, T., Miyasaka, K., Koyanagi, M., Tsunoda, T., Baba, I., Doi, K., ... Shirasawa, S. (2009). Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice. PloS one, 4(1), [e4240]. https://doi.org/10.1371/journal.pone.0004240

Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice. / Fujimoto, Takahiro; Miyasaka, Kyoko; Koyanagi, Midori; Tsunoda, Toshiyuki; Baba, Iwai; Doi, Keiko; Ohta, Minoru; Kato, Norihiro; Sasazuki, Takehiko; Shirasawa, Senji.

In: PloS one, Vol. 4, No. 1, e4240, 21.01.2009.

Research output: Contribution to journalArticle

Fujimoto, T, Miyasaka, K, Koyanagi, M, Tsunoda, T, Baba, I, Doi, K, Ohta, M, Kato, N, Sasazuki, T & Shirasawa, S 2009, 'Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice', PloS one, vol. 4, no. 1, e4240. https://doi.org/10.1371/journal.pone.0004240
Fujimoto T, Miyasaka K, Koyanagi M, Tsunoda T, Baba I, Doi K et al. Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice. PloS one. 2009 Jan 21;4(1). e4240. https://doi.org/10.1371/journal.pone.0004240
Fujimoto, Takahiro ; Miyasaka, Kyoko ; Koyanagi, Midori ; Tsunoda, Toshiyuki ; Baba, Iwai ; Doi, Keiko ; Ohta, Minoru ; Kato, Norihiro ; Sasazuki, Takehiko ; Shirasawa, Senji. / Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice. In: PloS one. 2009 ; Vol. 4, No. 1.
@article{2f70087758ec4dcb8c788ec559388429,
title = "Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice",
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.",
author = "Takahiro Fujimoto and Kyoko Miyasaka and Midori Koyanagi and Toshiyuki Tsunoda and Iwai Baba and Keiko Doi and Minoru Ohta and Norihiro Kato and Takehiko Sasazuki and Senji Shirasawa",
year = "2009",
month = "1",
day = "21",
doi = "10.1371/journal.pone.0004240",
language = "English",
volume = "4",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice

AU - Fujimoto, Takahiro

AU - Miyasaka, Kyoko

AU - Koyanagi, Midori

AU - Tsunoda, Toshiyuki

AU - Baba, Iwai

AU - Doi, Keiko

AU - Ohta, Minoru

AU - Kato, Norihiro

AU - Sasazuki, Takehiko

AU - Shirasawa, Senji

PY - 2009/1/21

Y1 - 2009/1/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=58749114217&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58749114217&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0004240

DO - 10.1371/journal.pone.0004240

M3 - Article

VL - 4

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - e4240

ER -