248 - Sex-specific metabolic changes during estrogen receptor beta activation in obesity. (ID 221)
Abstract
Background and Aims
Estrogens are important regulators of metabolic diseases including obesity and insulin resistance. The physiological and genomic signaling of estrogens is mainly mediated through the estrogen receptors (ER)α and ERβ. Although the role of ERβ in metabolism has recently gained attention, it is still unclear. However, no data report the different response to pharmaceutical activation of ERβ between sexes.
Methods
Female and male mice were fed a high fat diet (HFD) for 9 weeks while being treated with an ERβ selective ligand (DIP) for the last 3 weeks. The physiological response was investigated in vivo using magnetic resonance imaging and spectroscopy for adipose tissue distribution and hepatic triglycerides composition using the animal as its own control (before and after DIP). Gene and protein expression analysis was performed on harvested tissues.
Results
Response to DIP was sex-dependent and tissue-specific. Females showed improved metabolic profile and reduced liver steatosis. Moreover, DIP reduced the total body fat and increased the thermogenic activity of brown adipose tissue (BAT). In males, DIP provoked a shift of their fat distribution towards more subcutaneous fat depot including around the BAT. DIP treated males showed browning sites in the visceral adipose tissue and increased thermogenesis. Both sexes displayed hepatic lipid remodeling with less saturated and more unsaturated lipids after DIP.
Conclusions
Our data demonstrate that selective activation of ERβ has beneficial metabolic changes in obesity but these changes are sex dependent. Sex differences in ERβ activation represent an initial step towards a better understanding and development of sex-specific drugs.
