
OPN3 expressing neurons (inexperienced) within the paraventricular nucleus of the hypothalamus. Picture courtesy of Jonathan Mercado-Reyes. Credit score: Jonathan Mercado-Reyes.
Scientists found years in the past that the hypothalamus—which helps to handle physique temperature, starvation, intercourse drive, sleep and extra—consists of neurons that categorical the protein opsin 3 (OPN3). Far much less clear, nevertheless, was what this light-sensing protein does so deep contained in the mind.
A examine printed in PNAS means that OPN3 performs an essential position in regulating meals consumption.
“Our outcomes uncover a mechanism by which the nonvisual opsin receptor OPN3 modulates meals consumption by way of the melanocortin 4 receptor MC4R, which is essential for regulating power stability and feeding conduct,” stated Elena Oancea, a professor of medical science who’s affiliated with the Carney Institute for Mind Science at Brown College. “This discovering is attention-grabbing as a result of loss-of-function mutations in MC4R are a recognized genetic explanation for weight problems in people.”
The examine was led by Hala Haddad, who performed the analysis whereas a Ph.D. scholar after which postdoctoral analysis affiliate at Brown, with senior authors Oancea and Richard Lang, director of the Visible Methods Group at Cincinnati Kids’s.
The analysis workforce reported that OPN3 features along with MC4R and the Kir7.1 potassium channel to control sure cell alerts in addition to neuronal firing in a key space that controls power stability. Notably, when mice have been engineered to lack OPN3 on this a part of the hypothalamus, they ate considerably much less and have been much less energetic than management mice.
“We’re very excited to have, for the primary time, a mobile mechanism of what OPN3 is doing within the mind,” Oancea stated.
Opsin 3 has been the main target of analysis in Oancea’s lab for nearly a decade, and the workforce has found that it’s current in melanocytes, the place it features in pigmentation, and has developed a mouse mannequin to determine the particular mind areas the place this protein is expressed. Researchers in Lang’s lab have additionally been finding out OPN3 in fats tissue and within the mind, primarily utilizing mouse genetics instruments. The 2 analysis groups began collaborating round 2020.
Whereas their findings add an essential perception into the perform of OPN3, the researchers stated extra examine is important to handle whether or not the mechanism additionally performs in related methods within the human mind.
“Whereas we recognized the mechanism and performance of OPN3 on this area of the hypothalamus, how this receptor works in different areas of the mind stays elusive,” Oancea stated. “There have to be a typical paradigm for OPN3 perform in several areas, and we’re nonetheless on the lookout for that.”
Furthermore, “the present evaluation doesn’t resolve the query of whether or not OPN3 can perform as a lightweight sensor within the mouse mind,” Lang stated. “That continues to be to be addressed in future research.”
The regulation of consuming conduct and physique weight is extraordinarily complicated, Oancea stated.
“Determining the way to tackle these complicated points requires a broader understanding of the mobile processes concerned,” she stated.
Extra data:
Hala Okay. Haddad et al, Hypothalamic opsin 3 suppresses MC4R signaling and potentiates Kir7.1 to advertise meals consumption, Proceedings of the Nationwide Academy of Sciences (2025). DOI: 10.1073/pnas.2403891122
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