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Deletion of Lkb1 in adult mice results in body weight reduction and lethality

Liver kinase B1 (Lkb1) plays crucial roles in development, metabolism and survival. As constitutive knockout of Lkb1 in mice leads to embryonic lethality, whether Lkb1 is required for the growth and survival of adult mice is unclear. Here we address this question using a tamoxifen-inducible Lkb1 kno...

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Autores principales: Shan, Tizhong, Xiong, Yan, Kuang, Shihuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099919/
https://www.ncbi.nlm.nih.gov/pubmed/27824128
http://dx.doi.org/10.1038/srep36561
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author Shan, Tizhong
Xiong, Yan
Kuang, Shihuan
author_facet Shan, Tizhong
Xiong, Yan
Kuang, Shihuan
author_sort Shan, Tizhong
collection PubMed
description Liver kinase B1 (Lkb1) plays crucial roles in development, metabolism and survival. As constitutive knockout of Lkb1 in mice leads to embryonic lethality, whether Lkb1 is required for the growth and survival of adult mice is unclear. Here we address this question using a tamoxifen-inducible Lkb1 knockout (KO) mouse model: Rosa26-Cre(ER): Lkb1(flox/flox) (abbreviated as Rosa-Lkb1). The Rosa-Lkb1 mice exhibited body weight reduction and died within 6 weeks after tamoxifen induction. The body weight reduction was due to reduced weight of various tissues but the brown and white adipose tissues underwent much more pronounced weight reduction relative to the overall body weight reduction. Accordingly, the Rosa-Lkb1 mice had increased blood glucose levels and were intolerant to glucose challenge. Expression levels of adipogenic and lipogenic genes in adipose tissues were also dramatically reduced by Lkb1 deletion. Additionally, Lkb1 deletion reduced lipid deposition and increased expression of mitochondrial (Pgc1a, Cox5b and Cox7a) and hepatic gluconeogenesis related genes (Pepck) in liver. Finally, the Rosa-Lkb1 mice had much reduced oxygen consumption, carbon dioxide production, and energy expenditure. These results demonstrate that Lkb1 plays an important role in maintaining body weight, liver and adipose tissue function, blood glucose homeostasis and survival in adult mice.
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spelling pubmed-50999192016-11-14 Deletion of Lkb1 in adult mice results in body weight reduction and lethality Shan, Tizhong Xiong, Yan Kuang, Shihuan Sci Rep Article Liver kinase B1 (Lkb1) plays crucial roles in development, metabolism and survival. As constitutive knockout of Lkb1 in mice leads to embryonic lethality, whether Lkb1 is required for the growth and survival of adult mice is unclear. Here we address this question using a tamoxifen-inducible Lkb1 knockout (KO) mouse model: Rosa26-Cre(ER): Lkb1(flox/flox) (abbreviated as Rosa-Lkb1). The Rosa-Lkb1 mice exhibited body weight reduction and died within 6 weeks after tamoxifen induction. The body weight reduction was due to reduced weight of various tissues but the brown and white adipose tissues underwent much more pronounced weight reduction relative to the overall body weight reduction. Accordingly, the Rosa-Lkb1 mice had increased blood glucose levels and were intolerant to glucose challenge. Expression levels of adipogenic and lipogenic genes in adipose tissues were also dramatically reduced by Lkb1 deletion. Additionally, Lkb1 deletion reduced lipid deposition and increased expression of mitochondrial (Pgc1a, Cox5b and Cox7a) and hepatic gluconeogenesis related genes (Pepck) in liver. Finally, the Rosa-Lkb1 mice had much reduced oxygen consumption, carbon dioxide production, and energy expenditure. These results demonstrate that Lkb1 plays an important role in maintaining body weight, liver and adipose tissue function, blood glucose homeostasis and survival in adult mice. Nature Publishing Group 2016-11-08 /pmc/articles/PMC5099919/ /pubmed/27824128 http://dx.doi.org/10.1038/srep36561 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Shan, Tizhong
Xiong, Yan
Kuang, Shihuan
Deletion of Lkb1 in adult mice results in body weight reduction and lethality
title Deletion of Lkb1 in adult mice results in body weight reduction and lethality
title_full Deletion of Lkb1 in adult mice results in body weight reduction and lethality
title_fullStr Deletion of Lkb1 in adult mice results in body weight reduction and lethality
title_full_unstemmed Deletion of Lkb1 in adult mice results in body weight reduction and lethality
title_short Deletion of Lkb1 in adult mice results in body weight reduction and lethality
title_sort deletion of lkb1 in adult mice results in body weight reduction and lethality
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099919/
https://www.ncbi.nlm.nih.gov/pubmed/27824128
http://dx.doi.org/10.1038/srep36561
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