The researchers from the Scripps Research Institute, California, discovered that mice genetically altered to lack the EP3 receptor tended to be more active and eat more when they would normally be asleep, leading to weight increases of up to 30 per cent. The EP3 receptor is one of four receptors for prostaglandin E2 (PGE2), an important inflammatory mediator in both the central nervous system (CNS) and the periphery that controls fever, fertility and blood pressure. It has long been known that the absence of EP3 receptors prevents fever responses in mice, however, the researchers discovered that when the mice were four to five months old they started gaining weight. "The experimental mice were clearly getting heavier than their wild type litter mates, the control mice," said Sanchez-Alavez, one of the co-authors of the recent article in the 'Proceedings of the National Academy of Sciences'. "We realized there was something interesting going on with these animals, so we started watching their behaviour at night and during the day." The researchers noticed that the mice without the EP3 receptor were more active during the light hours, the 'night' for nocturnal mice, and were exhibiting increased feeding during this time. This increased feeding activity led to higher body temperatures, but the mice were still not burning enough calories to counter the additional eating - leading to the development of obese mice. These mice not only exhibited the body weight increases observed in obesity, but also increased levels of insulin, a hormone that regulates carbohydrate metabolism, and leptin, the hormone responsible for regulating energy intake and expenditure in the blood plasma. The body weight increase was accounted for by increases in abdominal and subcutaneous fat as well as increased liver weight. According to Sanchez-Alavez the next step will be to determine whether the obesity observed in the EP3 receptor deficient mice is due to the lack of EP3 in the CNS or in the peripheral organs. Sanchez-Alavez continued: "Something is happening there in that circuit; the PGE2 and leptin may be interacting and controlling eating behaviour." Dr Tamas Bartfai, lead author of the research and director of the Harold L. Dorris Neurological Research Centre at The Scripps Research Institute, said: "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."