Researchers identify estrogen-regulated brain circuit that helps females control obesity

Seeking to better understand the key role that the female hormone estrogen plays in maintaining energy balance and weight management, a group led by researchers at Baylor College of Medicine investigated the interactions of estrogen with specific regions of the brain that provide these anti-inflammatory benefits. obesity.

The team reveals in the diary. Progress of science a estrogen-activated neurocircuitry that stimulates thermogenesis, or production of body heat, and physical activity in animal models. The circuit starts at 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 estrogens, but also to changes in ambient temperature and in the nutritional status of the animal. Interestingly, the circuit appears to be functional in men but, at this point, its physiological relevance is unclear.

“My lab has long been interested in understanding sex differences in metabolic control,” said co-corresponding author Dr. Yong Xu, professor of pediatrics: nutrition and molecular and cell biology at Baylor. “For example, before menopause, women are generally protected from metabolic problems that can lead to weight gain, compared to men of the same age. However, after menopause, this benefit appears to disappear. Researchers around the world agree that estrogen is an important factor in this benefit.”

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

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

The researchers also found that the circuit responds to changes in room temperature and on the nutritional status of the animal.

“For example, the circuit can be activated in cold weather, 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 slow down thermogenesis and physical activity, saving energy to adapt to the lack of nutrients.”

Xu and his colleagues 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 they are stimulated. However, we still don’t know what role this circuit plays in males. More studies will help answer this question.”