A recent study reveals that opsin 3 (OPN3), a protein found in the hypothalamus, plays a key role in regulating food consumption and energy balance. The discovery sheds new light on the mechanisms controlling hunger and metabolism in the brain.
The study, published in Proceedings of the National Academy of Sciences (PNAS), identifies a critical pathway by which OPN3 interacts with the melanocortin 4 receptor (MC4R) and the Kir7.1 potassium channel to modulate neuronal activity and energy regulation. “This research uncovers a mechanism by which the nonvisual opsin receptor OPN3 modulates food intake via MC4R, which is crucial for regulating energy balance and feeding behavior,” said Elena Oancea, professor of medical science at Brown University’s Carney Institute for Brain Science. “This finding is particularly significant because loss-of-function mutations in MC4R are known to be a genetic cause of obesity in humans.”
The study was led by Hala Haddad, a Ph.D. student and later a postdoctoral researcher at Brown University, alongside senior authors Oancea and Richard Lang, director of the Visual Systems Group at Cincinnati Children’s. The research team found that when mice were genetically engineered to lack OPN3 in a specific part of the hypothalamus, they ate significantly less and were less active compared to control mice. This suggests that OPN3 is crucial for regulating feeding behavior and energy expenditure.
“We’re very excited to have, for the first time, a cellular mechanism of what OPN3 is doing in the brain,” Oancea said.
Opsin 3 has been a focus of research in Oancea’s lab for nearly a decade. The protein is known to play a role in pigmentation within melanocytes, and the team developed a mouse model to identify where OPN3 is expressed in the brain. In addition, Lang’s lab has been investigating OPN3 in both fat tissue and the brain, using genetic tools in mice. Their collaboration began in 2020.
While the findings provide important insights into OPN3’s function in energy regulation, the researchers emphasize that more research is needed to understand whether these mechanisms apply similarly in the human brain. “Although we have identified the mechanism and function of OPN3 in this region of the hypothalamus, its role in other areas of the brain remains unclear,” Oancea said. “We are still investigating whether there is a common paradigm for OPN3 function across different brain regions.”
Furthermore, the study does not yet resolve whether OPN3 acts as a light sensor in the mouse brain, an area that will be explored in future studies, according to Lang.
The regulation of eating behavior and body weight is a highly complex process, and Oancea emphasized the importance of gaining a broader understanding of the cellular mechanisms involved. “To address these complex issues, we need a deeper understanding of the cellular processes at play,” she concluded.
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