TY - JOUR
T1 - LGR4 is essential for R-spondin1-mediated suppression of food intake via pro-opiomelanocortin
AU - Otsuka, Ayano
AU - Jinguji, Ayana
AU - Maejima, Yuko
AU - Kasahara, Yoshiyuki
AU - Shimomura, Kenju
AU - Hidema, Shizu
AU - Nishimori, Katsuhiko
N1 - Funding Information:
This study was partly supported by a JSPS Grant-in-Aid for Scientific Research (A) [Grant Numbers 15H02442 (2015-2018), K.N.], and by a KAKENHI-Follow-up Grant Program supported by the Center for Gender Equality Promotion of Tohoku University (S.H.).
Publisher Copyright:
© 2019 Japan Society for Bioscience, Biotechnology, and Agrochemistry.
PY - 2019
Y1 - 2019
N2 - Leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4) suppresses food intake after its activation by binding of its ligands, R-spondins. We investigated the mechanism of food intake suppression by R-spondin1 in a region-specific Lgr4 gene knockout (LGR4 cKO) mouse model, generated by deletion of the Lgr4 gene in arcuate nucleus (ARC) using Lgr4fx/fx mice combined with infection of an AAV-Cre vector. After R-spondin1 administration, LGR4 cKO mice didn't exhibit a suppressed appetite, compared to that in control mice, which received a vehicle. In ARC of LGR4 cKO mice, Pomc mRNA expression was reduced, leading to suppressed food intake. On the other hand, neurons-specific LGR4 KO mice exhibited no differences in Pomc expression, and no structural differences were observed in the ARC of mutant mice. These results suggest that LGR4 is an essential part of the mechanism, inducing Pomc gene expression with R-spondin1 in ARC neurons in mice, thereby regulating feeding behavior.
AB - Leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4) suppresses food intake after its activation by binding of its ligands, R-spondins. We investigated the mechanism of food intake suppression by R-spondin1 in a region-specific Lgr4 gene knockout (LGR4 cKO) mouse model, generated by deletion of the Lgr4 gene in arcuate nucleus (ARC) using Lgr4fx/fx mice combined with infection of an AAV-Cre vector. After R-spondin1 administration, LGR4 cKO mice didn't exhibit a suppressed appetite, compared to that in control mice, which received a vehicle. In ARC of LGR4 cKO mice, Pomc mRNA expression was reduced, leading to suppressed food intake. On the other hand, neurons-specific LGR4 KO mice exhibited no differences in Pomc expression, and no structural differences were observed in the ARC of mutant mice. These results suggest that LGR4 is an essential part of the mechanism, inducing Pomc gene expression with R-spondin1 in ARC neurons in mice, thereby regulating feeding behavior.
KW - Arcuate nucleus
KW - Food intake
KW - LGR4
KW - POMC
KW - R-spondin1
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U2 - 10.1080/09168451.2019.1591266
DO - 10.1080/09168451.2019.1591266
M3 - Article
C2 - 30916623
AN - SCOPUS:85067903812
SN - 0916-8451
VL - 83
SP - 1336
EP - 1342
JO - Bioscience, Biotechnology and Biochemistry
JF - Bioscience, Biotechnology and Biochemistry
IS - 7
ER -