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

M. J. Vazquez, C. A. Toro, J. M. Castellano, F. Ruiz-Pino, J. Roa, D. Beiroa, V. Heras, I. Velasco, C. Dieguez, L. Pinilla, F. Gaytan, R. Nogueiras, M. A. Bosch, O. K. Rønnekleiv, A. Lomniczi (), S. R. Ojeda and M. Tena-Sempere ()
Additional contact information
M. J. Vazquez: Instituto Maimónides de Investigación Biomédica de Cordoba (IMIBIC)
C. A. Toro: Oregon National Primate Research Center/Oregon Health and Science University
J. M. Castellano: Instituto Maimónides de Investigación Biomédica de Cordoba (IMIBIC)
F. Ruiz-Pino: Instituto Maimónides de Investigación Biomédica de Cordoba (IMIBIC)
J. Roa: Instituto Maimónides de Investigación Biomédica de Cordoba (IMIBIC)
D. Beiroa: University of Santiago de Compostela-Instituto de Investigación Sanitaria
V. Heras: Instituto Maimónides de Investigación Biomédica de Cordoba (IMIBIC)
I. Velasco: Instituto Maimónides de Investigación Biomédica de Cordoba (IMIBIC)
C. Dieguez: Instituto de Salud Carlos III
L. Pinilla: Instituto Maimónides de Investigación Biomédica de Cordoba (IMIBIC)
F. Gaytan: Instituto Maimónides de Investigación Biomédica de Cordoba (IMIBIC)
R. Nogueiras: Instituto de Salud Carlos III
M. A. Bosch: Oregon Health and Science University
O. K. Rønnekleiv: Oregon Health and Science University
A. Lomniczi: Oregon National Primate Research Center/Oregon Health and Science University
S. R. Ojeda: Oregon National Primate Research Center/Oregon Health and Science University
M. Tena-Sempere: Instituto Maimónides de Investigación Biomédica de Cordoba (IMIBIC)

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract 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.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-06459-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06459-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-06459-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().