Amino acid sensing in hypothalamic tanycytes via umami taste receptors

Abstract

ObjectiveHypothalamic tanycytes are glial cells that line the wall of the third ventricle and contact the cerebrospinal fluid (CSF). While they are known to detect glucose in the CSF we now show that tanycytes also detect amino acids, important nutrients that signal satiety.MethodsCa2+ imaging and ATP biosensing were used to detect tanycyte responses to l-amino acids. The downstream pathway of the responses was determined using ATP receptor antagonists and channel blockers. The receptors were characterized using mice lacking the Tas1r1 gene, as well as an mGluR4 receptor antagonist.ResultsAmino acids such as Arg, Lys, and Ala evoke Ca2+ signals in tanycytes and evoke the release of ATP via pannexin 1 and CalHM1, which amplifies the signal via a P2 receptor dependent mechanism. Tanycytes from mice lacking the Tas1r1 gene had diminished responses to lysine and arginine but not alanine. Antagonists of mGluR4 greatly reduced the responses to alanine and lysine.ConclusionTwo receptors previously implicated in taste cells, the Tas1r1/Tas1r3 heterodimer and mGluR4, contribute to the detection of a range of amino acids by tanycytes in CSF.

Ablation of tanycytes of the arcuate nucleus and median eminence increases visceral adiposity and decreases insulin sensitivity in male mice

“…Beta-tanycytes have been reported to sense glucose and amino acids [15][16][17], and have been proposed to act as essential central integrators of metabolic regulation [5,13,14]. Nevertheless, tanycyte ablation did not result in dramatic changes in regulation of energy balance in normal and obesogenic dietary conditions.…”

“…Tanycytes also express many markers of neural progenitor cells, and have been reported to show limited neurogenic potential [10][11][12].Recently, there has been growing interest in the potential role of tanycytes in regulating energy metabolism [5,13,14]. Tanycytes have been reported to directly sense glucose and amino acid levels in CSF and blood [15][16][17], to actively transport leptin into the hypothalamus [18], and to regulate production and release of thyroid releasing hormone (TRH) [9,19]. However, these studies have not directly investigated whether tanycytes are indeed necessary for regulating these processes.…”

“…Previous studies have suggested a role for beta-tanycytes in the formation of the blood-hypothalamus barrier [2,3] and control of its permeability in response to dietary signals [4]. Both alpha-2 and beta-tanycytes have also been implicated in formation of the CSF-hypothalamus barrier [28] and in active transport of small molecules and proteins between the CSF and hypothalamic parenchyma [15,17]. We examined the permeability of both the blood-hypothalamus and CSF-hypothalamus barriers in tanycyteablated mice using Evans Blue, delivered via both intravenous (i.v.)…”

An integrative view of mammalian seasonal neuroendocrinology

“…Tanycytes are a specialised type of ependymal cells, which line the walls of the 3V and send long processes toward hypothalamic nuclei and the ME/PT region (Figure ). The strategic location of tanycytes at the interface between the cerebrospinal fluid and the pituitary blood flow at the ME suggests key functions in the blood‐brain barrier and in the selective transport of molecules between compartments and in nutrient sensing . Even though these cells were described over a century ago, and their morphology has been studied extensively, comparatively little is known regarding their functions .…”

“…The strategic location of tanycytes at the interface between the cerebrospinal fluid and the pituitary blood flow at the ME suggests key functions in the blood-brain barrier and in the selective transport of molecules between compartments 100,101 and in nutrient sensing. 102,103 Even though these cells were described over a century ago, and their morphology has been studied extensively, comparatively little is known regarding their functions. 101 Although this classification has been useful, recent data show that it largely undermines the diversity of tanycytes.…”