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

Abstract 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...

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Autores principales:	Shuiqing Qiu, Juliana Torrens Vazquez, Erin Boulger, Haiyun Liu, Ping Xue, Mehboob Ali Hussain, Andrew Wolfe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/36b06c8286404acf8816016885762bed
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spelling	oai:doaj.org-article:36b06c8286404acf8816016885762bed2021-12-02T15:06:20ZHepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males10.1038/s41598-017-01937-42045-2322https://doaj.org/article/36b06c8286404acf8816016885762bed2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01937-4https://doaj.org/toc/2045-2322Abstract 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 (E2) 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 (E2) 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 E2/ESR1 signaling plays a key role in the maintenance of gluconeogenesis and lipid metabolism in males.Shuiqing QiuJuliana Torrens VazquezErin BoulgerHaiyun LiuPing XueMehboob Ali HussainAndrew WolfeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shuiqing Qiu Juliana Torrens Vazquez Erin Boulger Haiyun Liu Ping Xue Mehboob Ali Hussain Andrew Wolfe Hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males
description	Abstract 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 (E2) 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 (E2) 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 E2/ESR1 signaling plays a key role in the maintenance of gluconeogenesis and lipid metabolism in males.
format	article
author	Shuiqing Qiu Juliana Torrens Vazquez Erin Boulger Haiyun Liu Ping Xue Mehboob Ali Hussain Andrew Wolfe
author_facet	Shuiqing Qiu Juliana Torrens Vazquez Erin Boulger Haiyun Liu Ping Xue Mehboob Ali Hussain Andrew Wolfe
author_sort	Shuiqing Qiu
title	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_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_sort	hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/36b06c8286404acf8816016885762bed
work_keys_str_mv	AT shuiqingqiu hepaticestrogenreceptoraiscriticalforregulationofgluconeogenesisandlipidmetabolisminmales AT julianatorrensvazquez hepaticestrogenreceptoraiscriticalforregulationofgluconeogenesisandlipidmetabolisminmales AT erinboulger hepaticestrogenreceptoraiscriticalforregulationofgluconeogenesisandlipidmetabolisminmales AT haiyunliu hepaticestrogenreceptoraiscriticalforregulationofgluconeogenesisandlipidmetabolisminmales AT pingxue hepaticestrogenreceptoraiscriticalforregulationofgluconeogenesisandlipidmetabolisminmales AT mehboobalihussain hepaticestrogenreceptoraiscriticalforregulationofgluconeogenesisandlipidmetabolisminmales AT andrewwolfe hepaticestrogenreceptoraiscriticalforregulationofgluconeogenesisandlipidmetabolisminmales
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Hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males

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