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 (E 2) deficiency. In mice, OVX decreased AT browning along with increased body weight, fat mass, and size of lipid droplets 12 weeks after surgery. Exogenous E 2 recovered the OVX-induced changes. AT browning was enhanced by M2 macrophages induced by exogenous E 2. E 2-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 E 2 enhances AT browning via M2 polarization mediated by HO-1.
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