Targeted disruption of G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) in mice.
G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) is a novel G protein-coupled receptor for bile acid. Tissue distribution and cell-type specificity of Gpbar1 mRNA suggest a potential role for the receptor in the endocrine system; however, the precise physiological role of Gpbar1 still remains to be elucidated. To investigate the role of Gpbar1 in vivo, the Gpbar1 gene was disrupted in mice. In homozygous mice, total bile acid pool size was significantly decreased by 21-25% compared with that of the wild-type mice, suggesting that Gpbar1 contributes to bile acid homeostasis. In order to assess the impact of Gpbar1 deficiency in bile acid homeostasis more precisely, Gpbar1 homozygous mice were fed a high-fat diet for 2 months. As a result, female Gpbar1 homozygous mice showed significant fat accumulation with body weight gain compared with that of the wild-type mice. These findings were also observed in heterozygous mice to the same extent. Although the precise mechanism for fat accumulation in female Gpbar1 homozygous mice remains to be addressed, these data indicate that Gpbar1 is a potential new player in energy homeostasis. Thus, Gpbar1-deficient mice are useful in elucidating new physiological roles for Gpbar1.
Maruyama
Takaharu
T
Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba, Ibaraki 300-2611, Japan.
Tanaka
Kenichi
K
Suzuki
Jun
J
Miyoshi
Hiroyuki
H
Harada
Naomoto
N
Nakamura
Takao
T
Miyamoto
Yasuhisa
Y
Kanatani
Akio
A
Tamai
Yoshitaka
Y
D000818:Animals; D001483:Base Sequence; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000032:analysis / Q000378:metabolism; D015152:Blotting, Northern / Q000379:methods; D001823:Body Composition; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D005260:Female; D005704:Gallbladder / Q000378:metabolism; D006706:Homeostasis; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D008969:Molecular Sequence Data; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014280:Triglycerides / Q000097:blood
D001647:Bile Acids and Salts; D004041:Dietary Fats; C513561:Gpbar1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D014280:Triglycerides; D002784:Cholesterol