Abstract
The central nervous system is critical in metabolic regulation, and accumulating evidence points to a distributed network of brain regions involved in energy homeostasis. This is accomplished, in part, by integrating peripheral and central metabolic information and subsequently modulating neuroendocrine outputs through the paraventricular and supraoptic nucleus of the hypothalamus. However, these hypothalamic nuclei are generally protected by a blood-brain-barrier limiting their ability to directly sense circulating metabolic signals—pointing to possible involvement of upstream brain nuclei. In this regard, sensory circumventricular organs (CVOs), brain sites traditionally recognized in thirst/fluid and cardiovascular regulation, are emerging as potential sites through which circulating metabolic substances influence neuroendocrine control. The sensory CVOs, including the subfornical organ, organum vasculosum of the lamina terminalis, and area postrema, are located outside the blood-brain-barrier, possess cellular machinery to sense the metabolic interior milieu, and establish complex neural networks to hypothalamic neuroendocrine nuclei. Here, evidence for a potential role of sensory CVO-hypothalamic neuroendocrine networks in energy homeostasis is presented.
Highlights
Precise and reciprocal interactions between the central nervous system (CNS) and peripheral organs plays an integral role in whole body metabolic homeostasis, and impairments in this CNS-peripheral communication are clearly implicated in the development of metabolic disorders
Within the CNS, a network of brain regions are involved in metabolic regulation, it is generally accepted that metabolic information from both peripheral and central inputs will eventually be integrated into the hypothalamus [4,5,7]
The majority of circulating factors cannot directly access these hypothalamic nuclei as they are protected by the blood-brain barrier (BBB) and/or substances are transported in limited quantity across the BBB; specialized endothelial cells located between the bloodstream and brain as a protective barrier against circulating toxins and pathogens [8,9]
Summary
Precise and reciprocal interactions between the central nervous system (CNS) and peripheral organs plays an integral role in whole body metabolic homeostasis, and impairments in this CNS-peripheral communication are clearly implicated in the development of metabolic disorders. The majority of circulating factors (hormones, adipokines, metabolites, etc.) cannot directly access these hypothalamic nuclei as they are protected by the blood-brain barrier (BBB) and/or substances are transported in limited quantity across the BBB; specialized endothelial cells located between the bloodstream and brain as a protective barrier against circulating toxins and pathogens [8,9] This suggests involvement of other brain region(s) upstream of the PVN/SON in neuroendocrine-dependent metabolic homeostasis. In this regard, the sensory circumventricular organs (CVOs) are a key candidate, considering that: (1) They are located outside the BBB; (2) They possess the cellular machinery to detect circulating.
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