Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice.
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.
Fujimoto
Takahiro
T
Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
Miyasaka
Kyoko
K
Koyanagi
Midori
M
Tsunoda
Toshiyuki
T
Baba
Iwai
I
Doi
Keiko
K
Ohta
Minoru
M
Kato
Norihiro
N
Sasazuki
Takehiko
T
Shirasawa
Senji
S
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D050154:Adiposity / Q000235:genetics; D000821:Animal Feed; D000818:Animals; D064429:Fatty Acid Synthases / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D009765:Obesity / Q000235:genetics* / Q000473:pathology
D007328:Insulin; C557477:KRAP protein, mouse; D008565:Membrane Proteins; D008840:Microfilament Proteins; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase; D005947:Glucose