Data from: Estrogen synthesized in the central nervous system enhances MC4R expression and reduces food intake

Estrogen is synthesized throughout various tissues in the body, and its
production is regulated by the rate-limiting enzyme aromatase (encoded by
the Cyp19a1 gene). Notably, aromatase is also expressed in central nervous
system cells, allowing for localized estrogen synthesis in regions such as
the hypothalamus. Estrogens produced within these neurons are referred to
as neuroestrogens. In this study, we investigated the role of
neuroestrogens in the regulation of appetite through modulation of
hypothalamic pathways in OVX, ArKO, and aromatase-restored mice. Estrogen
suppresses appetite by influencing the expression of appetite-regulating
peptides, including POMC and NPY, via MC4R. We explored the direct effects
of neuroestrogens, independent from ovarian estrogen, on appetite
suppression and the underlying molecular mechanisms. We monitored body
weight and food intake and evaluated the expression of Cyp19a1, Mc4r, and
other appetite-related genes. Our findings indicate that OVX and ArKO mice
exhibited increased body weight and food consumption, which correlated
with altered expression of Mc4r and Cyp19a1. Conversely, restoration of
Cyp19a1 expression in a neuron specific manner significantly decreased
food intake and increased Mc4r expression in the hypothalamus.
Furthermore, neuroestrogens enhanced leptin responsiveness. Our results
imply that neuroestrogens likely contribute to appetite regulation and may
be relevant for body weight reduction.