LGR4 is essential for R-spondin1-mediated suppression of food intake via pro-opiomelanocortin

Ayano Otsuka, Ayana Jinguji, Yuko Maejima, Yoshiyuki Kasahara, Kenju Shimomura, Shizu Hidema, Katsuhiko Nishimori

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1336-1342
Number of pages7
JournalBioscience, Biotechnology and Biochemistry
Volume83
Issue number7
DOIs
Publication statusPublished - 2019

Keywords

  • Arcuate nucleus
  • Food intake
  • LGR4
  • POMC
  • R-spondin1

ASJC Scopus subject areas

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

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