ERα governs a specific gene expression program and metabolic function in white adipose tissue.

The White Adipose Tissue (WAT) has a major influence on energy metabolic functions and expresses the estrogen receptor ERα. Ovariectomized mice or mice carrying an ERα knock-out gene (ERKO), have a higher risk of becoming obese and developing metabolic disorders such as diabetes or dyslipidemia. To identify the direct target genes of ERα in visceral WAT, we treated ovariectomized mice with estradiol (E2) for 2 hours and proceeded to a genome-wide analysis of ERα binding sites to systemically identify them. We demonstrate that the E2/ERα pathway increases the expression of genes involved in the balance between lipids and glucose catabolism, the energy expenditure through the TCA cycle and the respiratory membrane chain. ERα binding sites and gene expression analysis in visceral and subcutaneous WAT, brown adipose tissue and liver show a specific program for each tissue. Our results are consistent with E2/ERα signaling protecting against metabolic diseases such as obesity by regulating an important gene regulatory network that helps maintaining normal metabolic functions in WAT.