Estrogen-controlled neural circuit sheds light on obesity regulation in women

Scientists at the Baylor College of Medicine have found an estrogen-activated neurocircuit in the brain that stimulates thermogenesis, or body heat production, and physical activity in animal models. The findings may help researchers better understand the key role of estrogen in maintaining energy and weight control.

Estrogen, one of the two female sex hormones. promotes the storage of fat for healthy reproduction. When estrogen is balanced, the right amount of fat helps carry out female reproductive functions. However, when there’s too little or too much of the hormone, weight gain often results.

“My lab has long been interested in understanding sex differences in metabolic control,” says co-corresponding author Dr. Yong Xu, professor of pediatrics – nutrition and molecular and cellular biology at Baylor, in a statement. “For instance, before menopause women are typically protected from metabolic problems that may lead to weight gain, when compared to age-matched men. However, after menopause, this benefit seems to disappear. Researchers around the world agree that estrogen is one important player in this benefit.”

The risks of estrogen replacement therapy outweigh its effect on reducing obesity, the authors say. “That made us try to identify the specific site of the action of estrogen,” Xu adds. “That may help us develop treatments with more selective benefits.”

The hypothalamus is a small gland that controls the hormone system, located at the base of the brain. Within the hypothalamus is the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH) which is where the estrogen-activating circuit is located. The neurons within the vIVMH interact with estrogen via estrogen receptor-alpha (ER-alpha) and respond to the hormone by connecting to and communicating with serotonin-producing neurons located in another brain region called the dorsal raphe nucleus (DRN).

The circuit not only responds to estrogen, but also to changes in ambient temperature and in the nutritional status of the animal. “For example, the circuit can be activated when it’s cold, stimulating thermogenesis and physical activity, which would help the animal stay warm,” Xu says. “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.”

Interestingly, the circuit seems to be functional in males but, at this point, its physiological relevance is not clear.

“My lab has long been interested in understanding sex differences in metabolic control,” explains Xu. “For instance, before menopause women are typically protected from metabolic problems that may lead to weight gain, when compared to age-matched men. However, after menopause, this benefit seems to disappear. Researchers around the world agree that estrogen is one important player in this benefit.

“We found that the circuit is conserved in males – they have the same neurons that express ER-alpha and project into the same downstream brain regions. If the circuit is artificially activated in males, the same responses occur – thermogenesis and physical activity are stimulated. However, we still don’t know the role this circuit plays in males. Further studies will help answer this question.”

This study was published in Science Advances.

Article written by Rhonda Errabelli

Comments

  1. “Estrogen” isn’t just one hormone, it’s three: estrone, estriadiol, and estriol. They are similar, but have slightly different effects at different sites in the body (estriol is typically considered the most beneficial to overall health, but that’s a broad generalization).
    It would be interesting to know if all three types influence the brain receptor mentioned in the article, or one sub-type more than another, and whether a woman’s estrogen ratios make a difference in thermogenesis. Many women gain weight taking oral contraceptive pills, which typically contain estradiol; whether that relates to the mechanism described in the article, I have no idea.

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