Insufficient oestrogen receptors may cause obesity

A recent UT Southwestern Medical Center study found that oestrogen regulates energy expenditure, appetite and body weight, while insufficient oestrogen receptors in specific parts of the brain may lead to obesity.

"Oestrogen has a profound effect on metabolism," said Dr Deborah Clegg, associate professor of internal medicine and senior author of the study published in Cell Metabolism. "We hadn't previously thought of sex hormones as being critical regulators of food intake and body weight."

The mouse study is the first to show that oestrogen, acting through two hypothalamic neural centers in the brain, keeps female body weight in check by regulating hunger and energy expenditure.

Female mice lacking oestrogen receptor alpha – a molecule that sends oestrogen signals to neurons – in those parts of the brain became obese and developed related diseases, such as diabetes and heart disease.

Similar results were not seen in male mice, although researchers suspect other unknown oestrogen receptor sites in the brain play a similar role.

Specific oestrogen delivery

The findings are potentially important for millions of postmenopausal women, many of whom have decided against hormonal replacement therapy

The study could lead to new hormonal replacement therapies in which oestrogen is delivered to specific parts of the brain that regulate body weight, thereby avoiding the risks associated with full-body oestrogen delivery, such as breast cancer and stroke.

Doctors stopped routinely recommending long-term oestrogen therapy for menopausal women in 2002 when a Women's Health Initiative study showed the hormone also led to increased risk of cardiovascular disease.

"The role of oestrogen in postmenopausal women continues to remain uncertain," Dr Clegg said. "Current research is focused on the timing and the type of oestrogen supplementation that would be most beneficial to women.

Our findings further support a role for oestrogens in regulating body weight and energy expenditure, suggesting a benefit of oestrogen supplementation in postmenopausal women."

(EurekAlert, October 2011)

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