Activation of G protein-coupled estrogen receptor can yield negative energy balance in leptin resistant mice model So Hee Park1, Chul Hoon Kim2, and Obin Kwon1 1Department of Biomedical Science, Seoul National University College of Medicine, Seoul, Korea 2Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea Abstract Estrogen plays an important role in the control of energy homeostasis in the hypothalamus. Recently, our group suggested that G protein-coupled estrogen receptor (GPER) can be the estrogen receptor that mediates the anorexigenic effect of estrogen through the STAT3 pathway in the hypothalamus. In this study, we investigated whether this GPER-mediated anorexigenic effect can overcome the leptin resistance in which most forms of obesity are involved. To verify our hypothesis, we injected G-1 or ICI 182,780 (agonists of GPER) to ovariectomized female ERα knockout mice or male C57BL/6J mice by intracerebroventricular injection. These mice were monitored for body weight gain and food intake for 24 hrs, and their hypothalamic tissues were analyzed by immunohistochemistry. Female ERα knockout mice showed obese phenotype and leptin resistance. Administration of GPER agonists to these mice significantly decreased food intake and body weight gain. Double immunohistochemistry data exhibited that GPER activation increased the number of pSTAT3-immunoreactive pro-opiomelanocortin (POMC) neurons in the arcuate nucleus. These results suggest that GPER-mediated anorexigenic effect in hypothalamus might overcome leptin resistance in ERα-independent manner, which provides a novel basis for future therapeutic interventions of obesity.
You must be logged in and own this session in order to post comments.