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Hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males

Impaired estrogens action is associated with features of the metabolic syndrome in animal models and humans. We sought to determine whether disruption of hepatic estrogens action in adult male mice could recapitulate aspects of the metabolic syndrome to understand the mechanistic basis for the pheno...

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Autores principales: Qiu, Shuiqing, Vazquez, Juliana Torrens, Boulger, Erin, Liu, Haiyun, Xue, Ping, Hussain, Mehboob Ali, Wolfe, Andrew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431852/
https://www.ncbi.nlm.nih.gov/pubmed/28490809
http://dx.doi.org/10.1038/s41598-017-01937-4
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author Qiu, Shuiqing
Vazquez, Juliana Torrens
Boulger, Erin
Liu, Haiyun
Xue, Ping
Hussain, Mehboob Ali
Wolfe, Andrew
author_facet Qiu, Shuiqing
Vazquez, Juliana Torrens
Boulger, Erin
Liu, Haiyun
Xue, Ping
Hussain, Mehboob Ali
Wolfe, Andrew
author_sort Qiu, Shuiqing
collection PubMed
description Impaired estrogens action is associated with features of the metabolic syndrome in animal models and humans. We sought to determine whether disruption of hepatic estrogens action in adult male mice could recapitulate aspects of the metabolic syndrome to understand the mechanistic basis for the phenotype. We found 17β-estradiol (E(2)) inhibited hepatic gluconeogenic genes such as phosphoenolpyruvate carboxykinase 1 (Pck-1) and glucose 6-phosphatase (G6Pase) and this effect was absent in mice lacking liver estrogen receptor α (Esr1) (LERKO mice). Male LERKO mice displayed elevated hepatic gluconeogenic activity and fasting hyperglycemia. We also observed increased liver lipid deposits and triglyceride levels in male LERKO mice, resulting from increased hepatic lipogenesis as reflected by increased mRNA levels of fatty acid synthase (Fas) and acetyl-CoA carboxylase (Acc1). ChIP assay demonstrated estradiol (E(2)) induced ESR1 binding to Pck-1, G6Pase, Fas and Acc1 promoters. Metabolic phenotyping demonstrated both basal metabolic rate and feeding were lower for the LERKO mice as compared to Controls. Furthermore, the respiratory exchange rate was significantly lower in LERKO mice than in Controls, suggesting an increase in lipid oxidation. Our data indicate that hepatic E(2)/ESR1 signaling plays a key role in the maintenance of gluconeogenesis and lipid metabolism in males.
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spelling pubmed-54318522017-05-16 Hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males Qiu, Shuiqing Vazquez, Juliana Torrens Boulger, Erin Liu, Haiyun Xue, Ping Hussain, Mehboob Ali Wolfe, Andrew Sci Rep Article Impaired estrogens action is associated with features of the metabolic syndrome in animal models and humans. We sought to determine whether disruption of hepatic estrogens action in adult male mice could recapitulate aspects of the metabolic syndrome to understand the mechanistic basis for the phenotype. We found 17β-estradiol (E(2)) inhibited hepatic gluconeogenic genes such as phosphoenolpyruvate carboxykinase 1 (Pck-1) and glucose 6-phosphatase (G6Pase) and this effect was absent in mice lacking liver estrogen receptor α (Esr1) (LERKO mice). Male LERKO mice displayed elevated hepatic gluconeogenic activity and fasting hyperglycemia. We also observed increased liver lipid deposits and triglyceride levels in male LERKO mice, resulting from increased hepatic lipogenesis as reflected by increased mRNA levels of fatty acid synthase (Fas) and acetyl-CoA carboxylase (Acc1). ChIP assay demonstrated estradiol (E(2)) induced ESR1 binding to Pck-1, G6Pase, Fas and Acc1 promoters. Metabolic phenotyping demonstrated both basal metabolic rate and feeding were lower for the LERKO mice as compared to Controls. Furthermore, the respiratory exchange rate was significantly lower in LERKO mice than in Controls, suggesting an increase in lipid oxidation. Our data indicate that hepatic E(2)/ESR1 signaling plays a key role in the maintenance of gluconeogenesis and lipid metabolism in males. Nature Publishing Group UK 2017-05-10 /pmc/articles/PMC5431852/ /pubmed/28490809 http://dx.doi.org/10.1038/s41598-017-01937-4 Text en © The Author(s) 2017 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
Qiu, Shuiqing
Vazquez, Juliana Torrens
Boulger, Erin
Liu, Haiyun
Xue, Ping
Hussain, Mehboob Ali
Wolfe, Andrew
Hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males
title Hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males
title_full Hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males
title_fullStr Hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males
title_full_unstemmed Hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males
title_short Hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males
title_sort hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431852/
https://www.ncbi.nlm.nih.gov/pubmed/28490809
http://dx.doi.org/10.1038/s41598-017-01937-4
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