Can Targeting Estrogen Receptors Alleviate Binge Eating Disorder?Wednesday, September 3, 2014
Binge eating disorder, a loss of control of food intake accompanied by dysphoric mood alterations, is more common in women than in men and may account for as much as 40% of severe obesity seen at bariatric centres.
Strangely enough, a new study by Xuehong Cao and colleagues from Baylor College of Medicine, Houston, Texas, published in the Journal of Clinical Investigation, shows that targeting estrogen receptors in the serotonergic neurons of brain centres involved in appetite regulation may alleviate this behaviour, at least in mice.
Previous observations in humans that women with binge eating often suffer from menstrual irregularity, presumably due to impaired functions of ovarian hormones (e.g. estrogens) and that circulating 17β-estradiol levels are inversely associated with binge eating, prompted these investigators to study the role of estrogen in binge eating behaviours in ovarectomised mice.
While estrogen administration resulted in markedly reduced binge eating behaviour in these mice, this effect was absent in genetically modified mice that lacked the estrogen receptor-α (ERα) in the dorsal raphe nuclei (DRN), an area particularly rich in serotonin (5-HT) neurons known to be important in appetite regulation (and sleep).
The researchers also showed that a conjugate that combines GLP-1 and estrogen into one molecule is far more effective in reducing binge eating behaviour than GLP-1 alone (again, this effect was much reduced in ERα KO mice) suggesting that such a conjugate may be used to specifically target GLP-1 receptor neurons, thereby perhaps avoiding any potential adverse effects of estrogen administration.
Obviously, there is a long way from such initial observations in mice to safe and effective treatments in humans.
Nevertheless, these observations should open a new field of interest in finding more effective pharmacological treatments for binge eating disorders or perhaps even more “common-garden-variety” obesity in humans.
Cao X, Xu P, Oyola MG, Xia Y, Yan X, Saito K, Zou F, Wang C, Yang Y, Hinton A Jr, Yan C, Ding H, Zhu L, Yu L, Yang B, Feng Y, Clegg DJ, Khan S, DiMarchi R, Mani SK, Tong Q, & Xu Y (2014). Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice. The Journal of clinical investigation PMID: 25157819