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

Marko Matic1, Galyna Bryzgalova, Hui Gao

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

Plos One
|March 2, 2013
PubMed

Insights

Estrogen receptor alpha (ERα) in the liver is not responsible for insulin resistance in metabolic syndrome. Liver-selective ERα knockout mice showed no metabolic changes, challenging previous findings in total ERα knockout mice.

Area of Science:

  • Endocrinology
  • Metabolic Syndrome Research
  • Molecular Biology

Background:

  • Estrogenic signaling is increasingly linked to metabolic syndrome (MS).
  • Estrogen's beneficial effects on MS symptoms are known, but mechanisms are unclear.
  • Total estrogen receptor alpha (ERα) knockout (KO) mice previously showed hepatic insulin resistance.

Purpose of the Study:

  • To investigate if liver-specific ERα ablation replicates the metabolic phenotypes observed in total ERα KO mice.
  • To determine the role of hepatic ERα in insulin resistance associated with metabolic syndrome.

Main Methods:

  • Generated a liver-selective ERα knockout (LERKO) mouse model.
  • Confirmed efficient and selective reduction of ERα in the liver of LERKO mice.
  • Compared LERKO mice with wild-type controls under normal and high-fat diet conditions, assessing body weight, hormone profiles, and glucose/insulin response.

Main Results:

  • LERKO mice exhibited selective ERα reduction in the liver without altering body weight or hormone profiles.
  • No significant differences in insulin sensitivity or glucose response were observed between LERKO and control mice, even on a high-fat diet.
  • Hepatic gene expression profiles showed minimal changes in LERKO mice.

Conclusions:

  • Hepatic ERα is unlikely to be the primary cause of insulin resistance observed in total ERα KO mice.
  • These findings suggest that ERα's role in hepatic insulin resistance within metabolic syndrome may involve extrahepatic mechanisms or other estrogen receptor subtypes.

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