Brain-derived neurotrophic factor (BDNF) activates PI3K-AKT-mTOR signaling via hypothalamic TrkB receptors to reduce feeding in Siberian sturgeon (Acipenser baerii)

Abstract

Although Brain-derived neurotrophic factor (BDNF) has been identified as an orexigenic peptide in zebrafish, its role in regulating feeding behavior in other fish species is still unclear. This study aimed to investigate the regulatory role of BDNF in feeding behavior of Siberian sturgeon (Acipenser baerii). The bdnf and its receptor TrkB genes (Abbdnf and AbTrkB) of Siberian sturgeon were cloned and found to be most highly expressed in the hypothalamus. Short- and long-term fasting experiments showed that Abbdnf and AbTrkB mRNA levels decreased in the hypothalamus after fasting, but increased after refeeding, consistent with the pattern observed for anorexigenic peptides. The NGF(nerve growth factor) structural domain has an important role in mediating the binding of BDNF to the TrkB receptor. To explore the feeding regulatory role of BDNF, recombinant AbBDNFNGF protein was expressed using prokaryotic expression system. Intraperitoneal injection of AbBDNFNGF suppressed cumulative food intake at 1 h, 3 h, and 6 h after administration, and resulted in upregulation of anorexigenic peptides (pomc and leptin) mRNA and downregulation of orexigenic peptides (npy and agrp) mRNA in both central and peripheral tissues. Additionally, AbBDNFNGF injection led to activation of TrkB receptors and pi3k-akt-mtor signaling pathway in the hypothalamus. Overall, this study confirms the anorexigenic effect of BDNF in Siberian sturgeon.