Estrogen signaling and the Metabolic Syndrome: Targeting the hepatic ERalpha action

We have previously shown that total estrogen receptor alpha (ERalpha knockout (KO) mice exhibit hepatic insulin resistance. To investigate the contribution of hepatic ERalpha action for the observed phenotype, we established a liver-selective ERalphaKO mouse model, LERKO. We demonstrate that LERKO mice have efficient reduction of ERalpha 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 ERalpha action may not be the initiating factor for the previously identified hepatic insulin resistance in ERalphaKO mice.

6

Matic M, Bryzgalova G, Gao H, Antonson P, Humire P, Omoto Y, Portwood N, Pramfalk C, Efendic S, Berggren PO, Gustafsson JÅ, Dahlman-Wright K