Apelin-13 enhances arcuate POMC neuron activity via inhibiting M-current.

Dong Kun Lee,Jae Hoon Jeong,Seunghoon Oh,Young-Hwan Jo,Mark S Shapiro

doi:10.1371/journal.pone.0119457

Dong Kun Lee, Jae Hoon Jeong + Show 3 more

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https://doi.org/10.1371/journal.pone.0119457

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Abstract

The hypothalamus is a key element of the neural circuits that control energy homeostasis. Specific neuronal populations within the hypothalamus are sensitive to a variety of homeostatic indicators such as circulating nutrient levels and hormones that signal circulating glucose and body fat content. Central injection of apelin secreted by adipose tissues regulates feeding and glucose homeostasis. However, the precise neuronal populations and cellular mechanisms involved in these physiological processes remain unclear. Here we examine the electrophysiological impact of apelin-13 on proopiomelanocortin (POMC) neuron activity. Approximately half of POMC neurons examined respond to apelin-13. Apelin-13 causes a dose-dependent depolarization. This effect is abolished by the apelin (APJ) receptor antagonist. POMC neurons from animals pre-treated with pertussis toxin still respond to apelin, whereas the Gβγ signaling inhibitor gallein blocks apelin-mediated depolarization. In addition, the effect of apelin is inhibited by the phospholipase C and protein kinase inhibitors. Furthermore, single-cell qPCR analysis shows that POMC neurons express the APJ receptor, PLC-β isoforms, and KCNQ subunits (2, 3 and 5) which contribute to M-type current. Apelin-13 inhibits M-current that is blocked by the KCNQ channel inhibitor. Therefore, our present data indicate that apelin activates APJ receptors, and the resultant dissociation of the Gαq heterotrimer triggers a Gβγ-dependent activation of PLC-β signaling that inhibits M-current.

Highlights

Apelin is a peptide, originally isolated from bovine stomach extracts and binds to the orphan G-protein-coupled apelin (APJ) receptor [1]
It has been demonstrated that half of POMC neurons in the arcuate nucleus (ARC) express the APJ receptor and that activation of the APJ receptor induces the release of α-MSH in in vitro preparations [12]
We found that approximately half of POMC neurons responded to apelin-13 (100 nM) with a depolarization

Summary

Introduction

Originally isolated from bovine stomach extracts and binds to the orphan G-protein-coupled apelin (APJ) receptor [1]. Apelin is considered one of adipokines as it is synthesized and secreted by adipocytes. The expression of apelin in fat cells is strongly regulated by the nutritional status in rodents [2]. Recent studies have demonstrated that apelin-expressing cells are present in the brain, in particular the hypothalamus [3,4,5]. Apelin-positive cells and its cognate APJ receptors are found in the paraventricular nucleus.

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