ERa 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 ERa. Ovariectomized mice or mice carrying an ERa 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 ERa in visceral WAT, we treated ovariectomized mice with estradiol (E2) for 2 hours and proceeded to a genome-wide analysis of ERa binding sites to systemically identify them. We demonstrate that the E2/ERa 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. ERa 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/ERa signaling protecting against metabolic diseases such as obesity by regulating an important gene regulatory network that helps maintaining normal metabolic functions in WAT. Overall design: ChIP-seq and RNA-seq