Neuroestrogen’s Appetite-Suppressing Power

A recent study conducted by researchers from Fujita Health University in Japan has uncovered the role of neuroestrogen in regulating appetite, a discovery that could lead to new approaches in combating obesity. Neuroestrogen, a form of estrogen synthesized directly in the brain, has long been known to exist, but its precise function remained unclear until now.

Neuroestrogen and appetite control

Estrogens are traditionally associated with the reproductive system, primarily produced by the ovaries. However, it is now known that the brain also synthesizes these hormones through an enzyme called aromatase. This brain-specific estrogen, termed neuroestrogen, has been implicated in various brain functions, but its role in appetite regulation has not been fully explored.

Lead author Takanori Hayashi, Associate Professor at Fujita Health University School of Medicine, explains that the melanocortin-4 receptor (MC4R) in the brain plays a role in controlling food intake. The new research highlights that neuroestrogen may directly influence the expression of MC4R, leading to a reduction in hunger.

Study Methodology

The study team, which included Dr. Hayashi and Dr. Eiji Nishio from Fujita Health University, along with collaborators from Chiba University and Fukuoka University, used mouse models to investigate neuroestrogen’s role in appetite control. Mice that lacked ovaries (OVX) and aromatase (ArKO) displayed increased body weight and food consumption compared to control mice. This suggested that the absence of neuroestrogen might contribute to overeating and weight gain.

When the aromatase gene was selectively reactivated in the brains of the ArKO mice, the results were striking. The reactivated mice, known as BrTG-ArKO, ate less than the non-reactivated group and showed increased MC4R expression in the hypothalamus, indicating that neuroestrogen had a direct impact on hunger suppression.

Neuroestrogen’s interaction with leptin

The research also explored the relationship between neuroestrogen and leptin, a hormone that helps regulate food intake. The study found that the mice with reactivated neuroestrogen responded more effectively to leptin, further suggesting that neuroestrogen plays a role in enhancing the body’s natural appetite-suppressing mechanisms.

Hayashi explains that this increased responsiveness to leptin could be due to neuroestrogen's ability to modulate the brain's sensitivity to the hormone, offering a potential avenue for future appetite-regulating therapies.

Implications for obesity treatment and women’s health

As obesity rates continue to rise globally, the potential to target appetite regulation through neuroestrogen presents a promising new frontier in clinical research. By harnessing the brain’s own hormone system to control hunger, researchers aim to develop more effective treatments for obesity that may offer advantages over conventional methods.

The findings also have significant implications for women’s health. Understanding how neuroestrogen interacts with other hormones could lead to new ways of managing hormonal changes associated with menopause or postpartum weight gain. This discovery opens the door to more targeted and precise interventions in the future.

Reference: Hayashi T, Kumamoto K, Kobayashi T, et al. Estrogen synthesized in the central nervous system enhances MC4R expression and reduces food intake. The FEBS Journal. 2025. doi: 10.1111/febs.17426

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