Scientists have discovered years ago that the hypothalamus – which helps manage body temperature, hunger, sexual movement, sleep and others – includes neurons that express the opn 3 (OPN3) protein. Much less clear, however, was what this light -detecting protein makes so deep in the brain.
A study published in Pnas suggests that OPN3 plays an important role in regulating food consumption.
Our results reveal a mechanism by which the non -optical Opsin OPN3 regulates the intake of food through the 4 MC4R melanocortin receptor, which is vital to regulating energy balance and nutrition behavior. This finding is interesting because the MC4R function mutations are a well -known genetic cause of obesity in humans. ”
Elena Oancea, Professor of Medical Science, Cardi Institute for brain science, Brown University
The study was led by Hala Haddad, who conducted the research while being Ph.D. Student and then postdoctoral research partner in Brown, with senior writers Oncea and Richard Lang, director of the Visual Systems team at Cincinnati Children’s.
The research team said that OPN3 operates with the MC4R and the Kir7.1 Potassium channel to regulate certain cellular signals as well as neuronal triggering in a basic area that controls energy balance. Specifically, when the mice were designed so that they do not have OPN3 in this part of the hypothalamus, they ate significantly less and were less active than the control mice.
“We are very excited to have, for the first time, a cellular mechanism of what OPN3 is doing to the brain,” Oancea said.
Opsin 3 has been the focus of research in OANCEA’s workshop for almost a decade, and the team has discovered that it is present in the melanocytes, where it operates in color and has developed a mouse model to identify the specific areas of the brain where this protein is expressed. Researchers in the Lang laboratory have also studied OPN3 in fat and brain web, using mainly genetic mouse tools. The two research teams began to work together around 2020.
While their findings add an important picture of OPN3 operation, the researchers said that more study is needed to address whether the mechanism also performs in the human brain similarly.
“While we found the mechanism and operation of OPN3 in this area of the hypothalamus, the way this receptor operates in other areas of the brain remains vague,” Oancea said. “There must be a common example of OPN3 in different areas and we are still looking for it.”
In addition, “current analysis does not resolve the question of whether OPN3 can act as a light sensor in the mouse brain,” Lang said. “This remains to be treated in future studies.”
Adjusting nutrition and body weight is extremely complicated, Oncea said.
“Understanding how to deal with these complex issues requires a broader understanding of the cellular processes involved,” he said.
This study was backed by the Brown University imaging installation and the microscopy and the core of the processing of transgenic animals and genome at Cincinnati Children’s. Research funding came from the National Institutes of Health (R01AR076241, R01EY027077, R01EY032029, R01EY032752, R01EY032566 and R01EEE34456) and the National Foundation of Sciences, including sources.
Source:
Magazine report:
Haddad, HK, et al. (2025) Hypothalamic Opsin 3 suppresses MC4R signaling and strengthens Kir7.1 to promote food consumption. Pnas. Doi.org/10.1073/pnas.2403891122.
