TRPV1-Mediated Sensing of Sodium and Osmotic Pressure in POMC Neurons in the Arcuate Nucleus of the Hypothalamus

The central melanocortin system conducted by anorexigenic pro-opiomelanocortin (POMC) neurons and orexigenic agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus (ARC) not only regulates feeding behavior but also blood pressure. Excessive salt intake raises the Na<sup&...

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Main Authors: Boyang Zhang, Kazuomi Kario, Toshihiko Yada, Masanori Nakata
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/14/13/2600
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author Boyang Zhang
Kazuomi Kario
Toshihiko Yada
Masanori Nakata
author_facet Boyang Zhang
Kazuomi Kario
Toshihiko Yada
Masanori Nakata
author_sort Boyang Zhang
collection DOAJ
description The central melanocortin system conducted by anorexigenic pro-opiomelanocortin (POMC) neurons and orexigenic agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus (ARC) not only regulates feeding behavior but also blood pressure. Excessive salt intake raises the Na<sup>+</sup> concentration ([Na<sup>+</sup>]) in the cerebrospinal fluid (CSF) and worsens hypertension. The blood–brain barrier is immature in the ARC. Therefore, both AgRP and POMC neurons in the ARC have easy access to the electrolytes in the blood and can sense changes in their concentrations. However, the sensitivity of AgRP and POMC neurons to Na<sup>+</sup> remains unclear. This study aimed to explore how the changes in the extracellular Na<sup>+</sup> concentration ([Na<sup>+</sup>]) influence these neurons by measuring the cytosolic Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>) in the single neurons isolated from the ARC that were subsequently immunocytochemically identified as AgRP or POMC neurons. Both AgRP and POMC neurons responded to increases in both [Na<sup>+</sup>] and osmolarity in C57BL/6 mice. In contrast, in transient receptor potential vanilloid 1 (TRPV1) knockout (KO) mice, POMC neurons failed to respond to increases in both [Na<sup>+</sup>] and osmolarity, while they responded to high glucose and angiotensin II levels with increases in [Ca<sup>2+</sup>]<sub>i</sub>. Moreover, in KO mice fed a high-salt diet, the expression of POMC was lower than that in wild-type mice. These results demonstrate that changes in [Na<sup>+</sup>] and osmolarity are sensed by the ARC POMC neurons via the TRPV1-dependent mechanism.
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spelling doaj.art-78140cf9d0ed4f229aa88ab11ee522002023-12-03T14:15:56ZengMDPI AGNutrients2072-66432022-06-011413260010.3390/nu14132600TRPV1-Mediated Sensing of Sodium and Osmotic Pressure in POMC Neurons in the Arcuate Nucleus of the HypothalamusBoyang Zhang0Kazuomi Kario1Toshihiko Yada2Masanori Nakata3Department of Physiology, Faculty of Medicine, Wakayama Medical University, Kimiidera 811-1, Wakayama 641-8509, JapanDivision of Cardiovascular Medicine, Department of Medicine, Jichi Medical University, Yakushiji 3311-1, Shimotsuke 329-0498, JapanCenter for Integrative Physiology, Kansai Electric Power Medical Research Institute, 1-5-6 Minatojimaminamimachi, Chuou-ku, Kobe 650-0047, JapanDepartment of Physiology, Faculty of Medicine, Wakayama Medical University, Kimiidera 811-1, Wakayama 641-8509, JapanThe central melanocortin system conducted by anorexigenic pro-opiomelanocortin (POMC) neurons and orexigenic agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus (ARC) not only regulates feeding behavior but also blood pressure. Excessive salt intake raises the Na<sup>+</sup> concentration ([Na<sup>+</sup>]) in the cerebrospinal fluid (CSF) and worsens hypertension. The blood–brain barrier is immature in the ARC. Therefore, both AgRP and POMC neurons in the ARC have easy access to the electrolytes in the blood and can sense changes in their concentrations. However, the sensitivity of AgRP and POMC neurons to Na<sup>+</sup> remains unclear. This study aimed to explore how the changes in the extracellular Na<sup>+</sup> concentration ([Na<sup>+</sup>]) influence these neurons by measuring the cytosolic Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>) in the single neurons isolated from the ARC that were subsequently immunocytochemically identified as AgRP or POMC neurons. Both AgRP and POMC neurons responded to increases in both [Na<sup>+</sup>] and osmolarity in C57BL/6 mice. In contrast, in transient receptor potential vanilloid 1 (TRPV1) knockout (KO) mice, POMC neurons failed to respond to increases in both [Na<sup>+</sup>] and osmolarity, while they responded to high glucose and angiotensin II levels with increases in [Ca<sup>2+</sup>]<sub>i</sub>. Moreover, in KO mice fed a high-salt diet, the expression of POMC was lower than that in wild-type mice. These results demonstrate that changes in [Na<sup>+</sup>] and osmolarity are sensed by the ARC POMC neurons via the TRPV1-dependent mechanism.https://www.mdpi.com/2072-6643/14/13/2600melanocortin systemAgRPPOMCsodium sensingTRPV1blood pressure
spellingShingle Boyang Zhang
Kazuomi Kario
Toshihiko Yada
Masanori Nakata
TRPV1-Mediated Sensing of Sodium and Osmotic Pressure in POMC Neurons in the Arcuate Nucleus of the Hypothalamus
Nutrients
melanocortin system
AgRP
POMC
sodium sensing
TRPV1
blood pressure
title TRPV1-Mediated Sensing of Sodium and Osmotic Pressure in POMC Neurons in the Arcuate Nucleus of the Hypothalamus
title_full TRPV1-Mediated Sensing of Sodium and Osmotic Pressure in POMC Neurons in the Arcuate Nucleus of the Hypothalamus
title_fullStr TRPV1-Mediated Sensing of Sodium and Osmotic Pressure in POMC Neurons in the Arcuate Nucleus of the Hypothalamus
title_full_unstemmed TRPV1-Mediated Sensing of Sodium and Osmotic Pressure in POMC Neurons in the Arcuate Nucleus of the Hypothalamus
title_short TRPV1-Mediated Sensing of Sodium and Osmotic Pressure in POMC Neurons in the Arcuate Nucleus of the Hypothalamus
title_sort trpv1 mediated sensing of sodium and osmotic pressure in pomc neurons in the arcuate nucleus of the hypothalamus
topic melanocortin system
AgRP
POMC
sodium sensing
TRPV1
blood pressure
url https://www.mdpi.com/2072-6643/14/13/2600
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AT toshihikoyada trpv1mediatedsensingofsodiumandosmoticpressureinpomcneuronsinthearcuatenucleusofthehypothalamus
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