Leptin is required for hypothalamic regulation of miRNAs targeting POMC 3′UTR

Leptin is required for hypothalamic regulation of miRNAs targeting POMC 3′UTR

The central nervous system (CNS) monitors modifications in metabolic parameters or hormone levels and elicits adaptive responses such as food intake regulation. Particularly, within the hypothalamus, leptin modulates the activity of pro-opiomelanocortin (POMC) neurons which are critical regulators o...

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Main Authors: Derghal, Adel, Djelloul, Mehdi, Airault, Coraline, Pierre, Clément, Dallaporta, Michel, Troadec, Jean-Denis, Tillement, Vanessa, Tardivel, Catherine, Bariohay, Bruno, Trouslard, Jérôme, Mounien, Lourdes
Format: Online
Language:English
Published: Frontiers Media S.A. 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422035/
id pubmed-4422035
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spelling pubmed-44220352015-05-21 Leptin is required for hypothalamic regulation of miRNAs targeting POMC 3′UTR Derghal, Adel Djelloul, Mehdi Airault, Coraline Pierre, Clément Dallaporta, Michel Troadec, Jean-Denis Tillement, Vanessa Tardivel, Catherine Bariohay, Bruno Trouslard, Jérôme Mounien, Lourdes Neuroscience The central nervous system (CNS) monitors modifications in metabolic parameters or hormone levels and elicits adaptive responses such as food intake regulation. Particularly, within the hypothalamus, leptin modulates the activity of pro-opiomelanocortin (POMC) neurons which are critical regulators of energy balance. Consistent with a pivotal role of the melanocortin system in the control of energy homeostasis, disruption of the POMC gene causes hyperphagia and obesity. MicroRNAs (miRNAs) are short noncoding RNA molecules that post-transcriptionally repress the expression of genes by binding to 3′-untranslated regions (3′UTR) of the target mRNAs. However, little is known regarding the role of miRNAs that target POMC 3′UTR in the central control energy homeostasis. Particularly, their interaction with the leptin signaling pathway remain unclear. First, we used common prediction programs to search for potential miRNAs target sites on 3′UTR of POMC mRNA. This screening identified a set of conserved miRNAs seed sequences for mir-383, mir-384-3p, and mir-488. We observed that mir-383, mir-384-3p, and mir-488 are up-regulated in the hypothalamus of leptin deficient ob/ob mice. In accordance with these observations, we also showed that mir-383, mir-384-3p, and mir-488 were increased in db/db mice that exhibit a non-functional leptin receptor. The intraperitoneal injection of leptin down-regulated the expression of these miRNAs of interest in the hypothalamus of ob/ob mice showing the involvement of leptin in the expression of mir-383, mir-384-3p, and mir-488. Finally, the evaluation of responsivity to intracerebroventricular administration of leptin exhibited that a chronic treatment with leptin decreased mir-488 expression in hypothalamus of C57BL/6 mice. In summary, these results suggest that leptin modulates the expression of miRNAs that target POMC mRNA in hypothalamus. Frontiers Media S.A. 2015-05-06 /pmc/articles/PMC4422035/ /pubmed/25999818 http://dx.doi.org/10.3389/fncel.2015.00172 Text en Copyright © 2015 Derghal, Djelloul, Airault, Pierre, Dallaporta, Troadec, Tillement, Tardivel, Bariohay, Trouslard and Mounien. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Derghal, Adel
Djelloul, Mehdi
Airault, Coraline
Pierre, Clément
Dallaporta, Michel
Troadec, Jean-Denis
Tillement, Vanessa
Tardivel, Catherine
Bariohay, Bruno
Trouslard, Jérôme
Mounien, Lourdes
spellingShingle Derghal, Adel
Djelloul, Mehdi
Airault, Coraline
Pierre, Clément
Dallaporta, Michel
Troadec, Jean-Denis
Tillement, Vanessa
Tardivel, Catherine
Bariohay, Bruno
Trouslard, Jérôme
Mounien, Lourdes
Leptin is required for hypothalamic regulation of miRNAs targeting POMC 3′UTR
author_facet Derghal, Adel
Djelloul, Mehdi
Airault, Coraline
Pierre, Clément
Dallaporta, Michel
Troadec, Jean-Denis
Tillement, Vanessa
Tardivel, Catherine
Bariohay, Bruno
Trouslard, Jérôme
Mounien, Lourdes
author_sort Derghal, Adel
title Leptin is required for hypothalamic regulation of miRNAs targeting POMC 3′UTR
title_short Leptin is required for hypothalamic regulation of miRNAs targeting POMC 3′UTR
title_full Leptin is required for hypothalamic regulation of miRNAs targeting POMC 3′UTR
title_fullStr Leptin is required for hypothalamic regulation of miRNAs targeting POMC 3′UTR
title_full_unstemmed Leptin is required for hypothalamic regulation of miRNAs targeting POMC 3′UTR
title_sort leptin is required for hypothalamic regulation of mirnas targeting pomc 3′utr
description The central nervous system (CNS) monitors modifications in metabolic parameters or hormone levels and elicits adaptive responses such as food intake regulation. Particularly, within the hypothalamus, leptin modulates the activity of pro-opiomelanocortin (POMC) neurons which are critical regulators of energy balance. Consistent with a pivotal role of the melanocortin system in the control of energy homeostasis, disruption of the POMC gene causes hyperphagia and obesity. MicroRNAs (miRNAs) are short noncoding RNA molecules that post-transcriptionally repress the expression of genes by binding to 3′-untranslated regions (3′UTR) of the target mRNAs. However, little is known regarding the role of miRNAs that target POMC 3′UTR in the central control energy homeostasis. Particularly, their interaction with the leptin signaling pathway remain unclear. First, we used common prediction programs to search for potential miRNAs target sites on 3′UTR of POMC mRNA. This screening identified a set of conserved miRNAs seed sequences for mir-383, mir-384-3p, and mir-488. We observed that mir-383, mir-384-3p, and mir-488 are up-regulated in the hypothalamus of leptin deficient ob/ob mice. In accordance with these observations, we also showed that mir-383, mir-384-3p, and mir-488 were increased in db/db mice that exhibit a non-functional leptin receptor. The intraperitoneal injection of leptin down-regulated the expression of these miRNAs of interest in the hypothalamus of ob/ob mice showing the involvement of leptin in the expression of mir-383, mir-384-3p, and mir-488. Finally, the evaluation of responsivity to intracerebroventricular administration of leptin exhibited that a chronic treatment with leptin decreased mir-488 expression in hypothalamus of C57BL/6 mice. In summary, these results suggest that leptin modulates the expression of miRNAs that target POMC mRNA in hypothalamus.
publisher Frontiers Media S.A.
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422035/
_version_ 1613220088747393024

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