Obesity is one of the most common health problems across the globe. According to the Obesity Report from the World Health Organization (WHO)* 59% of all adults in Europe are either overweight or obese.
However, significant differences do exist: Before reaching menopause, women tend to suffer from metabolic diseases less frequently than men, which suggests that female sex hormones offer a protective function. Moreover, postmenopausal women are more prone to obesity compared with premenopausal women.
Researchers had already proven links between the effects of estrogen (the female sex hormone) and leptin (an appetite-suppressing hormone). Estradiol, the most effective natural form of estrogen, regulates the balance between energy intake and energy use by changing eating behavior. However, it was not understood exactly how this sex hormone works to combat obesity.

The CITED1 Protein Controls Key Functions in the Brain
A team led by Prof. Cristina Garcia-Carceres at the DZD partner institute Helmholtz Munich found CITED1 predominately in the nerve cells of the hypothalamus – a control center of the autonomous nervous system. In this area, the neurons show increased sensitivity to estradiol. Genetically modified female mice without CITED1 in the hypothalamus reacted significantly less to the appetite-suppressing hormone leptin. Their food intake was more in line with the higher value of male animals. This increased their risk of developing diet-related obesity. Their energy intake was greater than their energy use.

The study offers more insights into the sex-specific differences associated with being overweight or obese. Researchers now hope to use these findings as a basis upon which to develop sex-specific medication to combat obesity with fewer side effects.

*Source: https://apps.who.int/iris/bitstream/handle/10665/353747/9789289057738-eng.pdf

Original publication:
González-García et al. (2023) Estradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1. Cell Metab. (In Press).