title: Estrogen signalling and the metabolic syndrome: targeting the hepatic estrogen receptor alpha action.
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.
authors: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors: Marko
authors: M
authors: Matic
authors: Galyna
authors: G
authors: Bryzgalova
authors: Hui
authors: H
authors: Gao
authors: Per
authors: P
authors: Antonson
authors: Patricia
authors: P
authors: Humire
authors: Yoko
authors: Y
authors: Omoto
authors: Neil
authors: N
authors: Portwood
authors: Camilla
authors: C
authors: Pramfalk
authors: Suad
authors: S
authors: Efendic
authors: Per-Olof
authors: PO
authors: Berggren
authors: Jan-Åke
authors: JÅ
authors: Gustafsson
authors: Karin
authors: K
authors: Dahlman-Wright
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics; D059305:Diet, High-Fat; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D059467:Transcriptome / Q000235:genetics
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D007328:Insulin; D005947:Glucose