From The Labs

Male brain heeds message of female sex hormone


Dr. Yong Xu
Dr. Yong Xu

By Dipali Pathak

The estrogen receptor can be critical in preventing weight gain in female mammals and there also is strong evidence that the same receptor is important for body weight control in males. However, very little is known about where this receptor acts in the male brain.

In a report published today in the Journal of Clinical Investigation, researchers at the USDA/ARS Children’s Nutrition Research Center at Baylor College of Medicine and Texas Children’s Hospital have found that the site of action is the amygdala, an almond-shaped region located deep in the brain’s medial temporal lobe that is linked to fear and pleasure responses.

Knock out estrogen receptor

Dr. Yong Xu, assistant professor of pediatrics — nutrition at Baylor and senior author of the paper, and colleagues found that when they knocked out the estrogen receptor α in the amygdala of male mice, the animals became obese. When they did the opposite – overexpressed the receptor in the same region of the male brain – it prevented the development of obesity in the male mice, even when they were on a high-fat diet.

Xu and colleagues also demonstrated that a pharmacological agent or drug that delivers estrogen into this region of the brain could effectively decrease body weight in male mice.

They also found that the estrogen receptor α regulates body weight in this region primarily through stimulating physical activity, not by affecting appetite.

“The function of this receptor in the male brain is to stimulate physical activity and by doing so, contributes to the prevention of obesity,” said Xu.

Stimulate physical activity

He and his colleagues concluded that the neurons in the medial temporal lobe stimulate physical activity, which in turn prevents weight gain.

Xu said the next steps in the research will be to look into these cells to study the intracellular mechanisms by which they accomplish their tests and identify potential new targets for treatment. He and colleagues also hope to determine where this estrogen comes from in male brains.

Others who took part in the study include Pingwen Xu, Xuehong Cao, Yanlin He, Yongjie Yang, Kenji Saito, Chunmei Wang, Xiaofeng Yan, Antentor Othrell Hinton Jr., Fang Zou, Hongfang Ding, Yan Xia, Chunling Yan, Gang Shu, San-Pin Wu, Sophia Y. Tsai, Francesco J. DeMayo and Qi Wu of Baylor; Liangru Zhu of Baylor and Huazhong University of Science and Technology; Bin Yang and Richard DeMarchi of Indiana University; Yuxin Feng of Cincinnati Children’s Hospital Medical Center; Deborah J. Clegg of Cedars-Sinai Medical Center; Sohaib A. Khan of the University of Cincinnati College of Medicine; and Qingchun Tong of the University of Texas Health Science Center at Houston.

This work was supported by grants from the NIH (R01DK093587, R01DK101379, R00DK085330, P01 DK088761, T32CA059268, NIHDK59820, DK5U19DK062434 and R01DK092605), Marcadia Biotech, the American Diabetes Association, and American Heart Association awards.

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