On March 25, Professor Zhong Chen, College of Pharmaceutic Science Zhejiang University (CPS-ZJU) published the newest research entitledAn H2R-dependent medial septum histaminergic circuit mediates feeding behavior in Current Biology.

Novel targets for treating feeding-related diseases are of great importance, and histamine has long been considered an anorexigenic agent. However, understanding its functions in feeding in a circuit-specific way is still limited. Here, we report a medial septum (MS)-projecting histaminergic circuit mediating feeding behavior. This MS-projecting histaminergic circuit is functionally inhibited during food consumption, and bidirectionally modulates feeding behavior via downstream H2, but not H1, receptors on MS glutamatergic neurons. Further, we observed a pathological decrease of histamine 2 receptors (H2Rs) expression in MS glutamatergic neurons in diet-induced obesity (DIO) mice. Genetically, down-regulation of H2Rs expression in MS glutamatergic neurons accelerates body-weight gain. Importantly, chronic activation of H2Rs in MS glutamatergic neurons (with its clinical agonist amthamine) significantly slowed down the body-weight gain in DIO mice, providing a possible clinical utility to treat obesity. Together, our results demonstrate that this MS-projecting histaminergic circuit is critically involved in feeding, and H2Rs in MS glutamatergic neurons is a promising target for treating body-weight problems.

This work was carried out by Ph.D. student Lingyu Xu and Ph.D. student Wenkai Lin under the supervision of Professor Zhong Chen, CPS-ZJU. This work was also supported by Professor Yulong Li from Peking University.

Link:https://www.cell.com/current-biology/fulltext/S0960-9822(22)00401-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0960982222004018%3Fshowall%3Dtrue