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Menin liver-specific hemizygous mice challenged with high fat diet show increased weight gain and markers of metabolic impairment

OBJECTIVE: The menin tumor suppressor protein is abundantly expressed in the liver, although no function has been identified because of lack of tumor development in multiple endocrine neoplasia type 1 (Men1) null livers. We examine the phenotype of mice lacking one functional allele of Men1 (consist...

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Autores principales: Wuescher, L, Angevine, K, Patel, P R, Mensah-Osman, E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366066/
https://www.ncbi.nlm.nih.gov/pubmed/23168387
http://dx.doi.org/10.1038/nutd.2012.7
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author Wuescher, L
Angevine, K
Patel, P R
Mensah-Osman, E
author_facet Wuescher, L
Angevine, K
Patel, P R
Mensah-Osman, E
author_sort Wuescher, L
collection PubMed
description OBJECTIVE: The menin tumor suppressor protein is abundantly expressed in the liver, although no function has been identified because of lack of tumor development in multiple endocrine neoplasia type 1 (Men1) null livers. We examine the phenotype of mice lacking one functional allele of Men1 (consistent with the phenotype in humans with MEN1 syndrome) challenged with high fat diet (HFD) to elucidate a metabolic function for hepatic menin. METHODS: In this study, we challenged mice harboring a liver-specific hemizygous deletion of Men1 (HETs) alongside wild-type (WT) counterparts with HFD for 3 months and monitored the severity of metabolic changes. We demonstrate that the HET mice challenged with HFD for 3 months show an increased weight gain with decreased glucose tolerance compared with WT counterparts. Along with these changes, there was a more severe serum hormone profile involving increased serum insulin, glucose and glucagon, all hallmarks of the type 2 diabetic phenotype. In concert with increased serum hormones, we found that these mice have significantly increased liver triglycerides coupled with increased liver steatosis and inflammatory markers. Quantitative real-time PCR and western blotting studies show increases in enzymes involved with lipogenesis and hepatic glucose production. CONCLUSION: We conclude that hepatic menin is required for regulation of diet-induced metabolism, and our studies indicate a protective role for the Men1 gene in the liver when challenged with HFD.
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spelling pubmed-33660662012-06-04 Menin liver-specific hemizygous mice challenged with high fat diet show increased weight gain and markers of metabolic impairment Wuescher, L Angevine, K Patel, P R Mensah-Osman, E Nutr Diabetes Original Article OBJECTIVE: The menin tumor suppressor protein is abundantly expressed in the liver, although no function has been identified because of lack of tumor development in multiple endocrine neoplasia type 1 (Men1) null livers. We examine the phenotype of mice lacking one functional allele of Men1 (consistent with the phenotype in humans with MEN1 syndrome) challenged with high fat diet (HFD) to elucidate a metabolic function for hepatic menin. METHODS: In this study, we challenged mice harboring a liver-specific hemizygous deletion of Men1 (HETs) alongside wild-type (WT) counterparts with HFD for 3 months and monitored the severity of metabolic changes. We demonstrate that the HET mice challenged with HFD for 3 months show an increased weight gain with decreased glucose tolerance compared with WT counterparts. Along with these changes, there was a more severe serum hormone profile involving increased serum insulin, glucose and glucagon, all hallmarks of the type 2 diabetic phenotype. In concert with increased serum hormones, we found that these mice have significantly increased liver triglycerides coupled with increased liver steatosis and inflammatory markers. Quantitative real-time PCR and western blotting studies show increases in enzymes involved with lipogenesis and hepatic glucose production. CONCLUSION: We conclude that hepatic menin is required for regulation of diet-induced metabolism, and our studies indicate a protective role for the Men1 gene in the liver when challenged with HFD. Nature Publishing Group 2012-05 2012-05-28 /pmc/articles/PMC3366066/ /pubmed/23168387 http://dx.doi.org/10.1038/nutd.2012.7 Text en Copyright © 2012 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Wuescher, L
Angevine, K
Patel, P R
Mensah-Osman, E
Menin liver-specific hemizygous mice challenged with high fat diet show increased weight gain and markers of metabolic impairment
title Menin liver-specific hemizygous mice challenged with high fat diet show increased weight gain and markers of metabolic impairment
title_full Menin liver-specific hemizygous mice challenged with high fat diet show increased weight gain and markers of metabolic impairment
title_fullStr Menin liver-specific hemizygous mice challenged with high fat diet show increased weight gain and markers of metabolic impairment
title_full_unstemmed Menin liver-specific hemizygous mice challenged with high fat diet show increased weight gain and markers of metabolic impairment
title_short Menin liver-specific hemizygous mice challenged with high fat diet show increased weight gain and markers of metabolic impairment
title_sort menin liver-specific hemizygous mice challenged with high fat diet show increased weight gain and markers of metabolic impairment
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366066/
https://www.ncbi.nlm.nih.gov/pubmed/23168387
http://dx.doi.org/10.1038/nutd.2012.7
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