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Weight and Appetite Regulated by Estrogen in the Brain


Researchers at UT Southwestern Medical Center are the first to show that estrogen in the brain controls female body weight by regulating appetite and energy use. The findings of this mouse study are potentially important for postmenopausal women, who often gain weight once their estrogen levels plummet.

Estrogen receptors in the brain regulate energy balance

Ever since the results of the Women’s Health Initiative were released in 2002, physicians have stopped routinely recommending long-term use of estrogen for menopausal women because of the increased risk of heart disease, stroke, uterine cancer, and breast cancer.

Many experts have also generally agreed that weight gain after menopause is likely to occur regardless of whether do or don’t take hormone therapy. This new study, however, indicates that estrogen regulates energy use and that insufficient estrogen receptors in certain parts of the brain may lead to overweight and obesity.

Using mice, the investigators found that estrogen acts through two specific hypothalamic centers in the brain that appear to regulate energy balance in female mice, but not in male mice. Female mice that did not have estrogen receptor alpha--a molecule that sends estrogen signals to brain cells—in the specific parts of the brain identified by the researchers became obese and developed diabetes, heart disease, and related disorders.

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According to the study’s senior author, Dr. Deborah Clegg, associate professor of internal medicine, “We hadn’t previously thought of sex hormones as being critical regulators of food intake and body weight.” She also noted that “Estrogen has a profound effect on metabolism," and that "the role of estrogen in postmenopausal women continues to remain uncertain.”

Millions of postmenopausal women in the near future could benefit from this study, as these findings could help scientists develop new hormone replacement therapies that target estrogen to specific parts of the brain only. Since there are estrogen receptors throughout the body, currently available forms of hormone therapy can reach these receptors and thus pose the risks already mentioned. Estrogen receptors are most notably in the endometrium (uterine lining), breast, and ovaries, as well as the heart, kidneys, bones, and lungs.

The finding that weight and appetite are regulated by estrogen is an important one and is already prompting more research. Dr. Clegg noted that “current research is focused on the timing and the type of estrogen supplement that would be most beneficial to women.”

UT Southwestern Medical Center

Picture credit: Wikimedia Commons