Acyl-CoA binding domain-containing 7 (Acbd7) is a paralog gene of the diazepam-binding inhibitor/Acyl-CoA binding protein in which single nucleotide polymorphism has recently been associated with obesity in humans. In this report, we provide converging evidence indicating that a splice variant isoform of the Acbd7 mRNA is expressed and translated by some POMC and GABAergic-neurons in the hypothalamic arcuate nucleus (ARC). We have demonstrated that the ARC ACBD7 isoform was produced and processed into a bioactive peptide referred to as nonadecaneuropeptide (NDN) in response to catabolic signals. We have characterized NDN as a potent anorexigenic signal acting through an uncharacterized endozepine G protein-coupled receptor and subsequently via the melanocortin system. Our results suggest that ACBD7-producing neurons participate in the hypothalamic leptin signalling pathway. Taken together, these data suggest that ACBD7-producing neurons are involved in the hypothalamic control exerted on food intake and energy expenditure by the leptin-melanocortin pathway.
Animal experimentation: This study was performed in strict accordance with the recommendations in Canadian Guide for the Care and Use of Laboratory Animals. The protocol was approved by the Animal Ethic Committee (CPAUL) of the Laval University (Permit Number: #2013-019-3). All surgery was performed under Isoflurane anesthesia, and every effort was made to minimize suffering.
- Richard D Palmiter, Howard Hughes Medical Institute, University of Washington, United States
© 2016, Lanfray et al.
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