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Mimicking estrogen to target metabolism
Estrogen is known to have positive effects on obesity and metabolism. Here, Sharma et al. show that a small-molecule agonist of one of estrogen’s receptors, the G protein–coupled estrogen receptor (GPER), may have a similar, but more targeted potential as a therapeutic in metabolic disease. In ovariectomized mice, a model of postmenopausal obesity, G-1 agonist treatment increased energy expenditure and had beneficial effects on weight, adiposity, metabolism, and inflammation. However, unlike traditional estrogen replacement therapy, GPER agonism did not affect bone density or result in uterine feminizing effects. G-1 also elicited weight loss in ovariectomized mice on a high-fat diet and prevented weight gain in obese male mice.
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