Washington: A team of researchers looked at the interactions of estrogen with specific regions of the brain that provide anti-obesity benefits in women. The research has been published in the “Science Advances Journal”. The team revealed an estrogen-activated neurocircuit that stimulates thermogenesis, or the production of body heat and physical activity in animal models. The circuit begins in neurons located in a region of the hypothalamus called the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH). These neurons interact with estrogen through estrogen receptor alpha (ER-alpha) and respond to the hormone by connecting and communicating with serotonin-producing neurons located in another region of the brain called the dorsal raphe nucleus (DRN). ). The circuit responds not only to estrogen, but also to changes in ambient temperature and the nutritional status of the animal. Interestingly, the circuit appears to be functional in males but, at this stage, its physiological relevance is unclear.

“My lab has a long-standing interest in understanding sex differences in metabolic control,” said co-corresponding author Dr. Yong Xu, professor of pediatrics – nutrition and molecular and cellular biology at Baylor.

“For example, before menopause, women are generally protected against metabolic problems that can lead to weight gain compared to men of the same age. However, after menopause, this advantage seems to disappear. Researchers around the world agree that estrogen is a big player in this benefit,” Xu added.

In previous work, the researchers showed that one of the estrogen receptors, ER-alpha, is expressed in several regions of the brain, including the v1VMH of the hypothalamus. When v1VMH neurons expressing ER-alpha respond to estrogen, animals increase thermogenesis and physical activity. Both responses are beneficial because they increase energy expenditure, which can prevent obesity.

“What we didn’t know at the time were the neurocircuits that mediate these responses. Using modern neuroscience technology, we identified a neurocircuit that connects ER-alpha expressing neurons in the vlVMH region to neurons in the DRN region. We have confirmed that estrogen-mediated activation of this circuit actually stimulates thermogenesis and physical activity,” Xu said.

The researchers also discovered that the circuit reacts to changes in ambient temperature and the animal’s nutritional status.

“For example, the circuit can be activated when it is cold, stimulating thermogenesis and physical activity, which would help the animal stay warm,” Xu said.

“The circuit can be inhibited when the animal is hungry, which would shut down thermogenesis and physical activity, saving energy to adapt to the lack of nutrients,” Xu added.

Xu and his colleagues have studied this circuit in women, but also in men.

“We found that the circuit is conserved in men – they have the same neurons that express ER-alpha and project to the same downstream brain regions. If the circuit is artificially activated in men, the same responses occur – thermogenesis and physical activity are stimulated However, we still do not know the role this circuit plays in men, and further studies will help answer this question,” Xu said.

Other contributors to this research are Hui Ye, Bing Feng, Chunmei Wang, Kenji Saito, Yongjie Yang, Lucas Ibrahimi, Sarah Schaul, Nirali Patel, Leslie Saenz, Pei Luo, Penghua Lai, Valeria Torres, Maya Kota, Devin Dixit, Xing Cai. , Na Qu, Ilirjana Hyseni, Kaifan Yu, Yuwei Jiang, Qingchun Tong, Zheng Sun, Benjamin R. Arenkiel, Yanlin He, and Pingwen Xu. The authors are affiliated with Baylor College of Medicine, the University of Illinois at Chicago, the Louisiana State University System, or the University of Texas Health Science Center at Houston.