Hypothalamic tanycytes internalize ghrelin from the cerebrospinal fluid: Molecular mechanisms and functional implications

IF 7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Molecular Metabolism Pub Date : 2024-10-12 DOI:10.1016/j.molmet.2024.102046

Ivana M. Gomez , Maia Uriarte , Gimena Fernandez , Franco Barrile , Daniel Castrogiovanni , Sonia Cantel , Jean-Alain Fehrentz , Pablo N. De Francesco , Mario Perello

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引用次数: 0

Abstract

Objective

The peptide hormone ghrelin exerts potent effects in the brain, where its receptor is highly expressed. Here, we investigated the role of hypothalamic tanycytes in transporting ghrelin across the blood-cerebrospinal fluid (CSF) interface.

Methods

We investigated the internalization and transport of fluorescent ghrelin (Fr-ghrelin) in primary cultures of rat hypothalamic tanycytes, mouse hypothalamic explants, and mice. We also tested the impact of inhibiting clathrin-mediated endocytosis of ghrelin in the brain ventricular system on the orexigenic and locomotor effects of the hormone.

Results

In vitro, we found that Fr-ghrelin is selectively and rapidly internalized at the soma of tanycytes, via a GHSR-independent and clathrin-dependent mechanism, and then transported to the endfoot. In hypothalamic explants, we also found that Fr-ghrelin is internalized at the apical pole of tanycytes. In mice, Fr-ghrelin present in the CSF was rapidly internalized by hypothalamic β-type tanycytes in a clathrin-dependent manner, and pharmacological inhibition of clathrin-mediated endocytosis in the brain ventricular system prolonged the ghrelin-induced locomotor effects.

Conclusions

We propose that tanycyte-mediated transport of ghrelin is functionally relevant, as it may contribute to reduce the concentration of this peptide hormone in the CSF and consequently shortens the duration of its central effects.

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下丘脑澹细胞内化脑脊液中的胃泌素：分子机制和功能影响

目的肽类激素胃泌素在大脑中具有强效作用，其受体在大脑中高度表达。在此，我们研究了下丘脑澹细胞在通过血液-脑脊液（CSF）界面转运胃泌素中的作用：我们研究了荧光胃泌素（Fr-ghrelin）在大鼠下丘脑澹细胞原代培养物、小鼠下丘脑外植体和小鼠体内的内化和转运。我们还测试了在脑室系统中抑制凝集素介导的胃泌素内吞对激素的促矿物质效应和运动效应的影响：结果：在体外，我们发现Fr-ghrelin通过GHSR依赖性和凝集素依赖性机制被选择性地快速内化到澹细胞的体节，然后被转运到内足。在下丘脑外植体中，我们还发现 Fr-ghrelin 在澹细胞的顶极被内化。在小鼠体内，CSF中的Fr-ghrelin以一种凝集素依赖的方式被下丘脑β型澹红细胞快速内化，而药物抑制脑室系统中凝集素介导的内吞作用延长了ghrelin诱导的运动效应：我们认为胰泌素细胞介导的胃泌素转运与功能相关，因为它可能有助于降低这种肽类激素在脑脊液中的浓度，从而缩短其中枢效应的持续时间。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Metabolism ENDOCRINOLOGY & METABOLISM-

CiteScore

14.50

自引率

2.50%

发文量

219

审稿时长

43 days

期刊介绍： Molecular Metabolism is a leading journal dedicated to sharing groundbreaking discoveries in the field of energy homeostasis and the underlying factors of metabolic disorders. These disorders include obesity, diabetes, cardiovascular disease, and cancer. Our journal focuses on publishing research driven by hypotheses and conducted to the highest standards, aiming to provide a mechanistic understanding of energy homeostasis-related behavior, physiology, and dysfunction. We promote interdisciplinary science, covering a broad range of approaches from molecules to humans throughout the lifespan. Our goal is to contribute to transformative research in metabolism, which has the potential to revolutionize the field. By enabling progress in the prognosis, prevention, and ultimately the cure of metabolic disorders and their long-term complications, our journal seeks to better the future of health and well-being.