Estrogen may suppress the urge for binge eating by activating serotonin neurons in the dorsal raphe nuclei—where binge eating behaviors are believed to be regulated—according to an animal study in the August 25 Journal of Clinical Investigation.
“We can speculate that in women who develop binge eating who also happen to have irregular menstrual cycles, it is probably because their estrogen function is somehow damaged, which is what leads to the development of binge eating,” Dr. Xu said.
Consistent with data in humans, the researchers found that estrogen strongly inhibited binge eating in ovariectomized female mice. Using genetic mouse models, Dr. Xu and colleagues then found that the estrogen receptor-α, expressed by serotonin neurons in the brain, mediates the effect of estrogen to suppress binge eating.
“The significance is not only understanding the mechanism of how estrogen may modulate this behavior, but from a more therapeutic point of view, this would identify a potential target for estrogen therapy or modified estrogen therapy for treatment of this problem,” Dr. Xu said.
The Role of Serotonin Neurons in Binge Eating
“We are seeing a strong and rather consistent picture that ovarian hormones do play a role in risk for binge eating in women. But to date, we haven’t been able to nail down the brain pathways involved in this association,” commented Kelly L. Klump, PhD, Professor and Co-Director of the Michigan State University Twin Registry, Michigan State University, East Lansing, MI.
“These findings highlight a potentially very important role of serotonin neurons in a particular part of the brain (ie, the dorsal raphe nuclei) as one system that may mediate the effects of hormones on binge eating,” Dr. Klump said. “We’ve always known that the hormones likely didn’t directly impact risk—but we haven’t known the systems involved. This paper is a significant step forward in understanding those mediating brain pathways,” she said.
The findings could help explain the changes in emotional eating across the menstrual cycle found in a study by Dr. Klump and colleagues in the February 2013 issue of the Journal of Abnormal Psychology. “My hunch is that the mediating pathways will be many, rather than only a few, and will likely include dopamine and opioid systems as well. But the more we can isolate individual pathways, the closer we will be to understanding their interactions and interplay and the ways in which they coalesce to increase binge eating risk,” Dr. Klump said.
In addition, Dr. Klump and colleagues found the same hormonal risk factors for full-blown binge eating in a study published in the September issue of Clinical Psychological Science. “It looks like the pattern of hormone effects are very similar in emotional eating and binge eating. Given that, I think the mechanisms explored in this study [by Xu et al] could relate to both,” she said.
Findings Suggest Possible Treatments
Given the association between estrogen replacement therapy and an increased risk of breast cancer, Dr. Xu and colleagues developed a glucagon-like peptide-1–estrogen (GLP-1–estrogen) conjugate designed to carry the estrogen to the brain including the dorsal raphe nuclei, but to have minimal uptake by the breast tissue. Injection of this compound into the mice reduced binge-like eating, mainly because of the effects of estrogen and also partly because of the effects of GLP-1.
“There are a few studies showing that binge patients tend to have decreased GLP-1 in their blood, but nobody had shown that GLP-1 suppresses binge eating in animals or humans until now,” said Dr. Xu. “We showed that these two things, estrogen and GLP-1, work together to decrease binge eating and that GLP-1 can carry estrogen to this specific site to produce a benefit, but bypasses the breast tissue.”
These findings provide a strong case for an interventional drug that specifically acts on estrogen receptor-α in the serotonin region of the brain to treat binge eating, Dr. Xu said.
Cao X, Xu P, Oyola MG, Xia Y, et al. Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice. J Clin Invest. 2014 Aug 26. pii: 74726. doi: 10.1172/JCI74726. [Epub ahead of print]
Klump KL, Keel PK, Racine SE, et al. The interactive effects of estrogen and progesterone on changes in emotional eating across the menstrual cycle. J Abnorm Psychol. 2013;122(1):131-137.
Klump KL, Racine SE, Hildebrand B, et al. Influences of ovarian hormones on dysregulated eating: a comparison of associations in women with versus women without binge episodes. Clinical Psychological Science. 2014;2(5):545-559.