Estrogen enhances browning in adipose tissue by M2 macrophage polarization via heme oxygenase-1

Loss of ovarian function results in increased fat mass, leading to the accumulation of adipose tissue macrophages that participate in chronic inflammation. We hypothesized that ovariectomy (OVX)-induced increases in body weight and fat mass are associated with decreased adipose tissue (AT) browning due to estrogen (E₂ ) deficiency. In mice, OVX decreased AT browning along with increased body weight, fat mass, and size of lipid droplets 12 weeks after surgery. Exogenous E₂ recovered the OVX-induced changes. AT browning was enhanced by M2 macrophages induced by exogenous E_2. E₂ -induced M2 polarization occurred due to the increased expression of heme oxygenase-1 (HO-1) in macrophages, leading to decreased reactive oxygen species levels. Collectively, we demonstrated that E₂ enhances AT browning via M2 polarization mediated by HO-1.