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

08:00 EDT 2nd April 2019 | BioPortfolio

Summary of "The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system."

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 (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 diet-induced 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 supressed 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.

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This article was published in the following journal.

Name: The Journal of clinical investigation
ISSN: 1558-8238
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Medical and Biotech [MESH] Definitions

Peptides derived from pro-opiomelanocortin (POMC) which can stimulate MELANOCYTES or CORTICOTROPHS. Melanocortins include ACTH; ALPHA-MSH; and other peptides such as BETA-MSH and GAMMA-MSH, derived from other fragments of POMC. These peptides act through a variety of MELANOCORTIN RECEPTORS to control different functions including steroidogenesis, energy homeostasis, feeding, and skin pigmentation.

Nutritional support given via the alimentary canal or any route connected to the gastrointestinal system (i.e., the enteral route). This includes oral feeding, sip feeding, and tube feeding using nasogastric, gastrostomy, and jejunostomy tubes.

A melanocortin receptor subtype found primarily in MELANOCYTES. It shows specificity for ALPHA-MSH and ADRENOCORTICOTROPIC HORMONE. Loss of function mutations of the type 1 melanocortin receptor account for the majority of red hair and fair skin recessive traits in human.

A melanocortin receptor subtype found primarily in the ADRENAL CORTEX. It shows specificity for ADRENOCORTICOTROPIC HORMONE.

A melanocortin receptor subtype found primarily in BRAIN. It shows specificity for ALPHA-MSH; BETA-MSH and ADRENOCORTICOTROPIC HORMONE.

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