Involvement of the Orexinergic System in Feeding

Pilar Marcos,Rafael Coveñas

doi:10.3390/app12010086

Pilar Marcos, Rafael Coveñas

Open Access

https://doi.org/10.3390/app12010086

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Abstract

To know the processes involved in feeding, the dysregulation of hypothalamic neuropeptides promoting anorexigenic/orexigenic mechanisms must be investigated. Many neuropeptides are involved in this behavior and in overweight/obesity. Current pharmacological strategies for the treatment of obesity are unfortunately not very effective and, hence, new therapeutic strategies must be investigated and developed. Due to the crucial role played by orexins in feeding behavior, the aim of this review is to update the involvement of the orexinergic system in this behavior. The studies performed in experimental animal models and humans and the relationships between the orexinergic system and other substances are mentioned and discussed. Promising research lines on the orexinergic system are highlighted (signaling pathways, heterogeneity of the hypothalamic orexinergic neurons, receptor-receptor interaction, and sex differences). Each of the orexin 1 and 2 receptors plays a unique role in energy metabolism, exerting a differential function in obesity. Additional preclinical/clinical studies must be carried out to demonstrate the beneficial effects mediated by orexin receptor antagonists. Because therapies applied are in general ineffective when they are directed against a single target, the best option for successful anti-obesity treatments is the development of combination therapies as well as the development of new and more specific orexin receptor antagonists.

Highlights

The hypothalamus is a regulator center involved in the integration of multiple factors and in the regulation of numerous homeostatic functions
Excitatory neuropeptides produced in the lateral hypothalamus/perifornical region
Orexigenic peptides A and B originate from prepro-orexin, but the enzymes implicated in this mechanism are unknown

Summary

Introduction

The hypothalamus is a regulator center involved in the integration of multiple factors and in the regulation of numerous homeostatic functions. The control of energy balance is one of the most complex hypothalamic tasks, as it requires the coordinated participation of other brain regions and substances secreted by peripheral organs, such as the gastrointestinal tract or the adrenal glands. These peripheric signals send information to the central nervous system about the state of the energy stores, affecting the energy intake and expenditure [1,2,3]. The balance between food intake and energy expenditure determines long-term energy homeostasis [1]

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