Determining why the lack of EP3 receptors causes increased activity and eating will likely take a great deal of experimentation. "It's a very complex phenomenon to explore," says Sanchez-Alavez. He notes that the next step in the research will be to determine whether the obese phenotype observed in the EP3 receptor deficient mice is dependent on the lack of EP3 in the central nervous system and/or peripheral organs, as EP3 is expressed in both locations.
The research has interesting implications for scientists' understanding of appetite regulation. PGE2 is known to stimulate the release of leptin-an important hormone secreted by white fat cells and a suppressor of appetite. However, in this model, lack of EP3 did not prevent leptin increase. "Something is happening there in that circuit," says Sanchez-Alavez. "The PGE2 and leptin may be interacting and controlling eating behavior."
Bartfai notes, "Inflammation as part of the obesity and metabolic syndrome is being recognized to an increasing degree. These data directly couple the lack of a particular type of inflammatory signaling via EP3R with leptin and insulin increase, glucose tolerance, and white fat accumulation, and thus may provide a very important animal model for determining the importance of inflammation in obesity and in the conversion of obesity to type 2 diabetes."
Ultimately, better understanding of the role of EP3 receptors in feeding and obesity could lead to the development of treatments that could prevent or reverse these conditions.
Along with Sanchez-Alavez and Bartfai, Izabella Klein, Sara Brownell, Iustin Tabarean, Christopher Davis, and Bruno Conti, all of Scripps Research, were authors on the paper, "Night eating and obesity in the EP3R deficient mouse."