The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system

Authors: Bouyakdan, Khalil; Martin, Hugo; Liénard, Fabienne; Budry, Lionel; Taib, Bouchra; Rodaros, Demetra; Chrétien, Chloé; Biron, Éric; Husson, Zoé; Cota, Daniela; Pénicaud, Luc; Fulton, Stephanie; Fioramonti, Xavier; Alquier, Thierry
Abstract: Glial cells have emerged as key players in the central control of energy balance and etiology of obesity. Astrocytes play a central role in neural communication via the release of gliotransmitters. Acyl-CoA–binding protein–derived (ACBP-derived) endozepines are secreted peptides that modulate the GABAA receptor. In the hypothalamus, ACBP is enriched in arcuate nucleus (ARC) astrocytes, ependymocytes, and tanycytes. Central administration of the endozepine octadecaneuropeptide (ODN) reduces feeding and improves glucose tolerance, yet the contribution of endogenous ACBP in energy homeostasis is unknown. We demonstrated that ACBP deletion in GFAP+ astrocytes, but not in Nkx2.1-lineage neural cells, promoted dietinduced hyperphagia and obesity in both male and female mice, an effect prevented by viral rescue of ACBP in ARC astrocytes. ACBP+ astrocytes were observed in apposition with proopiomelanocortin (POMC) neurons, and ODN selectively activated POMC neurons through the ODN GPCR but not GABAA, and suppressed feeding while increasing carbohydrate utilization via the melanocortin system. Similarly, ACBP overexpression in ARC astrocytes reduced feeding and weight gain. Finally, the ODN GPCR agonist decreased feeding and promoted weight loss in ob/ob mice. These findings uncover ACBP as an ARC gliopeptide playing a key role in energy balance control and exerting strong anorectic effects via the central melanocortin system.
Document Type: Article de recherche
Issue Date: 2 April 2019
Open Access Date: 11 June 2019
Document version: VoR
Permalink: http://hdl.handle.net/20.500.11794/35156
This document was published in: Journal of Clinical Investigation, Vol. 130 (6), 2417-2430 (2019)
https://doi.org/10.1172/JCI123454
American Society for Clinical Investigation
Alternative version: 10.1172/JCI123454
30938715
Collection:Articles publiés dans des revues avec comité de lecture

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