Cargando…
Leptin Signaling in Kiss1 Neurons Arises after Pubertal Development
The adipocyte-derived hormone leptin is required for normal pubertal maturation in mice and humans and, therefore, leptin has been recognized as a crucial metabolic cue linking energy stores and the onset of puberty. Several lines of evidence have suggested that leptin acts via kisspeptin expressing...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591417/ https://www.ncbi.nlm.nih.gov/pubmed/23505551 http://dx.doi.org/10.1371/journal.pone.0058698 |
_version_ | 1782262052467769344 |
---|---|
author | Cravo, Roberta M. Frazao, Renata Perello, Mario Osborne-Lawrence, Sherri Williams, Kevin W. Zigman, Jeffery M. Vianna, Claudia Elias, Carol F. |
author_facet | Cravo, Roberta M. Frazao, Renata Perello, Mario Osborne-Lawrence, Sherri Williams, Kevin W. Zigman, Jeffery M. Vianna, Claudia Elias, Carol F. |
author_sort | Cravo, Roberta M. |
collection | PubMed |
description | The adipocyte-derived hormone leptin is required for normal pubertal maturation in mice and humans and, therefore, leptin has been recognized as a crucial metabolic cue linking energy stores and the onset of puberty. Several lines of evidence have suggested that leptin acts via kisspeptin expressing neurons of the arcuate nucleus to exert its effects. Using conditional knockout mice, we have previously demonstrated that deletion of leptin receptors (LepR) from kisspeptin cells cause no puberty or fertility deficits. However, developmental adaptations and system redundancies may have obscured the physiologic relevance of direct leptin signaling in kisspeptin neurons. To overcome these putative effects, we re-expressed endogenous LepR selectively in kisspeptin cells of mice otherwise null for LepR, using the Cre-loxP system. Kiss1-Cre LepR null mice showed no pubertal development and no improvement of the metabolic phenotype, remaining obese, diabetic and infertile. These mice displayed decreased numbers of neurons expressing Kiss1 gene, similar to prepubertal control mice, and an unexpected lack of re-expression of functional LepR. To further assess the temporal coexpression of Kiss1 and Lepr genes, we generated mice with the human renilla green fluorescent protein (hrGFP) driven by Kiss1 regulatory elements and crossed them with mice that express Cre recombinase from the Lepr locus and the R26-tdTomato reporter gene. No coexpression of Kiss1 and LepR was observed in prepubertal mice. Our findings unequivocally demonstrate that kisspeptin neurons are not the direct target of leptin in the onset of puberty. Leptin signaling in kisspeptin neurons arises only after completion of sexual maturation. |
format | Online Article Text |
id | pubmed-3591417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35914172013-03-15 Leptin Signaling in Kiss1 Neurons Arises after Pubertal Development Cravo, Roberta M. Frazao, Renata Perello, Mario Osborne-Lawrence, Sherri Williams, Kevin W. Zigman, Jeffery M. Vianna, Claudia Elias, Carol F. PLoS One Research Article The adipocyte-derived hormone leptin is required for normal pubertal maturation in mice and humans and, therefore, leptin has been recognized as a crucial metabolic cue linking energy stores and the onset of puberty. Several lines of evidence have suggested that leptin acts via kisspeptin expressing neurons of the arcuate nucleus to exert its effects. Using conditional knockout mice, we have previously demonstrated that deletion of leptin receptors (LepR) from kisspeptin cells cause no puberty or fertility deficits. However, developmental adaptations and system redundancies may have obscured the physiologic relevance of direct leptin signaling in kisspeptin neurons. To overcome these putative effects, we re-expressed endogenous LepR selectively in kisspeptin cells of mice otherwise null for LepR, using the Cre-loxP system. Kiss1-Cre LepR null mice showed no pubertal development and no improvement of the metabolic phenotype, remaining obese, diabetic and infertile. These mice displayed decreased numbers of neurons expressing Kiss1 gene, similar to prepubertal control mice, and an unexpected lack of re-expression of functional LepR. To further assess the temporal coexpression of Kiss1 and Lepr genes, we generated mice with the human renilla green fluorescent protein (hrGFP) driven by Kiss1 regulatory elements and crossed them with mice that express Cre recombinase from the Lepr locus and the R26-tdTomato reporter gene. No coexpression of Kiss1 and LepR was observed in prepubertal mice. Our findings unequivocally demonstrate that kisspeptin neurons are not the direct target of leptin in the onset of puberty. Leptin signaling in kisspeptin neurons arises only after completion of sexual maturation. Public Library of Science 2013-03-07 /pmc/articles/PMC3591417/ /pubmed/23505551 http://dx.doi.org/10.1371/journal.pone.0058698 Text en © 2013 Cravo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Cravo, Roberta M. Frazao, Renata Perello, Mario Osborne-Lawrence, Sherri Williams, Kevin W. Zigman, Jeffery M. Vianna, Claudia Elias, Carol F. Leptin Signaling in Kiss1 Neurons Arises after Pubertal Development |
title | Leptin Signaling in Kiss1 Neurons Arises after Pubertal Development |
title_full | Leptin Signaling in Kiss1 Neurons Arises after Pubertal Development |
title_fullStr | Leptin Signaling in Kiss1 Neurons Arises after Pubertal Development |
title_full_unstemmed | Leptin Signaling in Kiss1 Neurons Arises after Pubertal Development |
title_short | Leptin Signaling in Kiss1 Neurons Arises after Pubertal Development |
title_sort | leptin signaling in kiss1 neurons arises after pubertal development |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591417/ https://www.ncbi.nlm.nih.gov/pubmed/23505551 http://dx.doi.org/10.1371/journal.pone.0058698 |
work_keys_str_mv | AT cravorobertam leptinsignalinginkiss1neuronsarisesafterpubertaldevelopment AT frazaorenata leptinsignalinginkiss1neuronsarisesafterpubertaldevelopment AT perellomario leptinsignalinginkiss1neuronsarisesafterpubertaldevelopment AT osbornelawrencesherri leptinsignalinginkiss1neuronsarisesafterpubertaldevelopment AT williamskevinw leptinsignalinginkiss1neuronsarisesafterpubertaldevelopment AT zigmanjefferym leptinsignalinginkiss1neuronsarisesafterpubertaldevelopment AT viannaclaudia leptinsignalinginkiss1neuronsarisesafterpubertaldevelopment AT eliascarolf leptinsignalinginkiss1neuronsarisesafterpubertaldevelopment |