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SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression

Puberty is regulated by epigenetic mechanisms and is highly sensitive to metabolic and nutritional cues. However, the epigenetic pathways mediating the effects of nutrition and obesity on pubertal timing are unknown. Here, we identify Sirtuin 1 (SIRT1), a fuel-sensing deacetylase, as a molecule that...

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Autores principales: Vazquez, M. J., Toro, C. A., Castellano, J. M., Ruiz-Pino, F., Roa, J., Beiroa, D., Heras, V., Velasco, I., Dieguez, C., Pinilla, L., Gaytan, F., Nogueiras, R., Bosch, M. A., Rønnekleiv, O. K., Lomniczi, A., Ojeda, S. R., Tena-Sempere, M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179991/
https://www.ncbi.nlm.nih.gov/pubmed/30305620
http://dx.doi.org/10.1038/s41467-018-06459-9
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author Vazquez, M. J.
Toro, C. A.
Castellano, J. M.
Ruiz-Pino, F.
Roa, J.
Beiroa, D.
Heras, V.
Velasco, I.
Dieguez, C.
Pinilla, L.
Gaytan, F.
Nogueiras, R.
Bosch, M. A.
Rønnekleiv, O. K.
Lomniczi, A.
Ojeda, S. R.
Tena-Sempere, M.
author_facet Vazquez, M. J.
Toro, C. A.
Castellano, J. M.
Ruiz-Pino, F.
Roa, J.
Beiroa, D.
Heras, V.
Velasco, I.
Dieguez, C.
Pinilla, L.
Gaytan, F.
Nogueiras, R.
Bosch, M. A.
Rønnekleiv, O. K.
Lomniczi, A.
Ojeda, S. R.
Tena-Sempere, M.
author_sort Vazquez, M. J.
collection PubMed
description Puberty is regulated by epigenetic mechanisms and is highly sensitive to metabolic and nutritional cues. However, the epigenetic pathways mediating the effects of nutrition and obesity on pubertal timing are unknown. Here, we identify Sirtuin 1 (SIRT1), a fuel-sensing deacetylase, as a molecule that restrains female puberty via epigenetic repression of the puberty-activating gene, Kiss1. SIRT1 is expressed in hypothalamic Kiss1 neurons and suppresses Kiss1 expression. SIRT1 interacts with the Polycomb silencing complex to decrease Kiss1 promoter activity. As puberty approaches, SIRT1 is evicted from the Kiss1 promoter facilitating a repressive-to-permissive switch in chromatin landscape. Early-onset overnutrition accelerates these changes, enhances Kiss1 expression and advances puberty. In contrast, undernutrition raises SIRT1 levels, protracts Kiss1 repression and delays puberty. This delay is mimicked by central pharmacological activation of SIRT1 or SIRT1 overexpression, achieved via transgenesis or virogenetic targeting to the ARC. Our results identify SIRT1-mediated inhibition of Kiss1 as key epigenetic mechanism by which nutritional cues and obesity influence mammalian puberty.
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spelling pubmed-61799912018-10-15 SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression Vazquez, M. J. Toro, C. A. Castellano, J. M. Ruiz-Pino, F. Roa, J. Beiroa, D. Heras, V. Velasco, I. Dieguez, C. Pinilla, L. Gaytan, F. Nogueiras, R. Bosch, M. A. Rønnekleiv, O. K. Lomniczi, A. Ojeda, S. R. Tena-Sempere, M. Nat Commun Article Puberty is regulated by epigenetic mechanisms and is highly sensitive to metabolic and nutritional cues. However, the epigenetic pathways mediating the effects of nutrition and obesity on pubertal timing are unknown. Here, we identify Sirtuin 1 (SIRT1), a fuel-sensing deacetylase, as a molecule that restrains female puberty via epigenetic repression of the puberty-activating gene, Kiss1. SIRT1 is expressed in hypothalamic Kiss1 neurons and suppresses Kiss1 expression. SIRT1 interacts with the Polycomb silencing complex to decrease Kiss1 promoter activity. As puberty approaches, SIRT1 is evicted from the Kiss1 promoter facilitating a repressive-to-permissive switch in chromatin landscape. Early-onset overnutrition accelerates these changes, enhances Kiss1 expression and advances puberty. In contrast, undernutrition raises SIRT1 levels, protracts Kiss1 repression and delays puberty. This delay is mimicked by central pharmacological activation of SIRT1 or SIRT1 overexpression, achieved via transgenesis or virogenetic targeting to the ARC. Our results identify SIRT1-mediated inhibition of Kiss1 as key epigenetic mechanism by which nutritional cues and obesity influence mammalian puberty. Nature Publishing Group UK 2018-10-10 /pmc/articles/PMC6179991/ /pubmed/30305620 http://dx.doi.org/10.1038/s41467-018-06459-9 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Vazquez, M. J.
Toro, C. A.
Castellano, J. M.
Ruiz-Pino, F.
Roa, J.
Beiroa, D.
Heras, V.
Velasco, I.
Dieguez, C.
Pinilla, L.
Gaytan, F.
Nogueiras, R.
Bosch, M. A.
Rønnekleiv, O. K.
Lomniczi, A.
Ojeda, S. R.
Tena-Sempere, M.
SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression
title SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression
title_full SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression
title_fullStr SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression
title_full_unstemmed SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression
title_short SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression
title_sort sirt1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling kiss1 expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179991/
https://www.ncbi.nlm.nih.gov/pubmed/30305620
http://dx.doi.org/10.1038/s41467-018-06459-9
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