L-Glutamate Regulates Npy via the mGluR4-Ca²⁺-ERK1/2 Signaling Pathway in Mandarin Fish (Siniperca chuatsi)

Metabotropic glutamate receptor 4 (mGluR4) is widely regarded as an umami receptor activated by L-glutamate to exert essential functions. Numerous studies have shown that umami receptors participate in food intake regulation. However, little is known about mGluR4's role in mediating food ingestion and its possible molecular mechanism. Mandarin fish, a typical carnivorous fish, is sensitive to umami substances and is a promising vertebrate model organism for studying the umami receptor. In this study, we identified the mGluR4 gene and conducted evolutionary analyses from diverse fish species with different feeding habits. mGluR4 of mandarin fish was cloned and functionally expressed to investigate the effects of L-glutamate on mGluR4. We further explored whether the signal pathway mGluR4-Ca²⁺-ERK1/2 participates in the process in mandarin fish brain cells. The results suggest that L-glutamate could regulate Neuropeptide Y (Npy) via the mGluR4-Ca²⁺-ERK1/2 signaling pathway in mandarin fish. Our findings unveil the role of mGluR4 in feeding decisions and its possible molecular mechanisms in carnivorous fishes.