Characterization of an anorexigenic hypothalamic neuron population producing an endozepine-like protein called ACBD7

The diazepam-binding inhibitor (DBI) and its related peptide, the octadecaneuropeptide (ODN), have originally been characterized for their ability to displace benzodiazepines from their binding site, i.e., the GABAA receptor. More recently, the ODN has been characterized as potent anorexigenic compound in rodents by acting via an uncharacterized endozepine GPCR. Although DBI was originally described as a neuronal produced protein, its gene is now recognized as exclusively expressed by glial cells, i.e. tanycytes and astrocytes, in the mammalian central nervous system. Recently, we demonstrated that a well conserved paralog gene of Dbi, called Acbd7, is also expressed, translated and processed into a potent anorexigenic peptide called nonadecaneuropeptide (NDN) in the rodent hypothalamus. Immunohistochemical investigation revealed that ACBD7 is exclusively produced by GABAergic neurons diverging from POMC and NPY/AgRP-producing neurons in the arcuate nucleus. Pharmacological experiments indicate that NDN also acts via the uncharacterized endozepine GPCR to decrease food intake and stimulate thermogenesis. Finally, our investigations indicate that ACBD7-producing neurons should act as a relay between the leptin and the melanocortin signaling pathway.