Brain estrogen appears as a hunger battle hero

According to pioneering research by Japanese scientists, the estrogen produced by the brain itself within the brain may be key to controlling appetite and resisting obesity, and these studies challenge the routine understanding of this key hormone.

Although most chaperone estrogens are associated with reproduction and ovarian function, researchers have found that it is also synthesized directly in the brain through an enzyme called aromatase. This locally produced “neuroestrogen” appears to play a direct role in regulating appetite by enhancing the expression of key receptors involved in starvation control.

“It is well known that MC4R (melanin-4 receptor) is an important receptor in the brain that regulates food intake,” explains Takanori Hayashi, associate professor at the School of Medicine, Fogeta Health University, Japan.

When aromatase function is specifically activated in the brains of mice that otherwise cannot produce estrogen, animals have significantly less food than foods without aromatase. These brain-recovered mice also showed a significant increase in MC4R expression in the hypothalamus, which is the core of appetite regulation.

The research team, in collaboration with Chiba University and Fukuoka University, published their findings in the FEBS Journal on February 18, 2025.

To study the specific effects of neuroestrogen, scientists have adopted several specialized mouse models. They compared mice lacking ovary (OVX), mice lacking aromatase (Arko) and specially engineered strains, where aromatase function (BRTG-ARKO) was restored only in the brain.

The results are surprising. When aromatase function is specifically activated in the brains of mice that otherwise cannot produce estrogen, animals have significantly less food than foods without aromatase. These brain-recovered mice also showed a significant increase in MC4R expression in the hypothalamus, which is the core of appetite regulation.

This pattern remains true in multiple experimental settings. Mice lacking ovarian or aromatase showed increased body weight and food consumption compared to normal mice. Researchers observed that only restoring the brain’s ability to produce estrogen can reverse these effects on appetite.

In addition to its direct effects on hunger regulation, the study reveals another fascinating mechanism: Neuroestrogen appears to enhance the brain’s response to leptin, a hormone produced by adipocytes that helps to fill the signal.

“We observed that mice with restored neuroestrogen respond more effectively to leptin treatment,” explains Dr. Hayashi. “This may be because neuroestrogen enhances the mechanisms of natural appetite suppression in the human body.”

To confirm their findings at the cellular level, the researchers conducted other experiments showing that neuroestrogen directly increased MC4R levels in hypothalamic neurons. This provides compelling evidence that appetite suppression is mediated locally in the brain, rather than ovarian-dependent estrogen.

The impact on obesity treatment may be important. As global obesity rates continue to climb, many conventional weight loss treatments have shown limited long-term success, providing a promising new approach to the brain’s own hormonal system.

These findings may be particularly important in understanding weight fluctuations associated with female hormone changes, including weight changes associated with menopause, naturally occurring.

“Neuroestrogen may be an appetite-changing game and dealing with obesity, and may be a game-changer,” Dr. Hayashi said in celebration of their discovery.

By discovering how neuroestrogen interacts with other appetite-regulating systems in the brain, researchers hope to develop innovative treatments to address hunger in their nervous system, potentially opening up new avenues for new ways to manage obesity and related metabolic diseases.