Estrogen signalling and the metabolic syndrome: targeting the hepatic estrogen receptor alpha action

Marko Matic; Galyna Bryzgalova; Hui Gao; Per Antonson; Patricia Humire; Yoko Omoto; Neil Portwood; Camilla Pramfalk; Suad Efendic; Per-Olof Berggren; Jan-Åke Gustafsson; Karin Dahlman-Wright

doi:10.1371/journal.pone.0057458

Estrogen signalling and the metabolic syndrome: targeting the hepatic estrogen receptor alpha action

PLoS One. 2013;8(2):e57458. doi: 10.1371/journal.pone.0057458. Epub 2013 Feb 25.

Authors

Marko Matic¹, Galyna Bryzgalova, Hui Gao, Per Antonson, Patricia Humire, Yoko Omoto, Neil Portwood, Camilla Pramfalk, Suad Efendic, Per-Olof Berggren, Jan-Åke Gustafsson, Karin Dahlman-Wright

Affiliation

¹ Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.

Abstract

An increasing body of evidence now links estrogenic signalling with the metabolic syndrome (MS). Despite the beneficial estrogenic effects in reversing some of the MS symptoms, the underlying mechanisms remain largely undiscovered. We have previously shown that total estrogen receptor alpha (ERα) knockout (KO) mice exhibit hepatic insulin resistance. To determine whether liver-selective ablation of ERα recapitulates metabolic phenotypes of ERKO mice we generated a liver-selective ERαKO mouse model, LERKO. We demonstrate that LERKO mice have efficient reduction of ERα selectively within the liver. However, LERKO and wild type control mice do not differ in body weight, and have a comparable hormone profile as well as insulin and glucose response, even when challenged with a high fat diet. Furthermore, LERKO mice display very minor changes in their hepatic transcript profile. Collectively, our findings indicate that hepatic ERα action may not be the responsible factor for the previously identified hepatic insulin resistance in ERαKO mice.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Body Weight / genetics
Diet, High-Fat
Estrogen Receptor alpha / genetics
Estrogen Receptor alpha / metabolism*
Estrogens / genetics
Estrogens / metabolism*
Glucose / metabolism
Insulin / metabolism
Liver / metabolism*
Metabolic Syndrome / genetics
Metabolic Syndrome / metabolism*
Mice
Mice, Inbred C57BL
Mice, Knockout
Signal Transduction
Transcriptome / genetics

Substances

Estrogen Receptor alpha
Estrogens
Insulin
Glucose

Grants and funding

This work is supported by the Swedish Research Council (http://www.vr.se/; The involvement of estrogen receptor signaling in insulin resistance and type 2 diabetes (project # K2009-54X-21122-01-3), Estrogen signaling in metabolic disease; a functional genomics approach (project # K2008-54X-20640-01-3) and Tissue-specific estrogen signaling - new insights in metabolic disease development (project # K2011-54X-20640-04-6)), Cancerfonden (http://www.cancerfonden.se; grant # 080482, 090678, 100404 and 110588), Novo Nordisk Foundation (http://www.novonordiskfonden.dk/en/; Estrogen signaling in metabolic disease (2006), Molecular mechanisms underlying the regulation of body weight and the anti-diabetic effects of estrogen (2008), Genetic dissection of estrogen signaling in mice (2009), Genetic dissection of estrogen signaling in metabolic disease (2011)), the Strategic Research Area in Diabetes at the Karolinska Institute (http://ki.se/srp-diabetes; SFO/TM Diabetes (2010)), Center for Biosciences (http://ki.se/cb; grant # n/a (2009–2011)), the KI Endomet network (http://researchnetworks.ki.se/converis/; grant details n/a), King Gustaf V and Queen Victoria's Freemason's Foundation (http://www.frimurarorden.se; Molecular Mechanisms Underlying the Antidiabetic Effects of Estrogen (2008, 2009, 2010, 2011)); and BioCrine AB (website and grant details n/a). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.