Diosmetin Protects Against Obesity and Metabolic Dysfunctions Through Activation of Adipose Estrogen Receptors in Mice
Baocai Xie, Dengke Pan, Huan Liu, Min Liu, Xiaochen Shi, Xinyi Chu, Jun Lu, Mengqing Zhu, Bo Xia, Jiangwei Wu
Abstract
SCOPE: Obesity is a major public health and economic problem of global significance. Here, we investigate the role of diosmetin, a natural flavonoid presents mainly in citrus fruits, in the regulation of obesity and metabolic dysfunctions in mice. METHODS AND RESULTS: daily) or vehicle for 8 weeks. Diosmetin treatment decreases body weight and fat mass, improves glucose tolerance and insulin resistance in obese mice. These metabolic benefits are mainly attributed to increase energy expenditure via enhancing thermogenesis in brown adipose tissue (BAT) and browning of white adipose tissue (WAT). Mechanistically, diosmetin acts as an agonist for estrogen receptors (ERs), and subsequently elevates adipose expressions of ERs in mice and in cultured adipocytes. When ERs are blocked by their antagonist fulvestrant in mice, diosmetin loses its beneficial effects, suggesting that ERs are indispensable for the metabolic benefits of diosmetin. CONCLUSION: The results indicate that diosmetin may be a potential anti-obesity nutritional supplement and could be explored for low ERs-related obesity populations.