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Scripps research team discovers a chemical pathway that causes mice to overeat and gain weight

The Scripps Research team, led by neuroscientists Manuel Sanchez-Alavez and Tamas Bartfai, discovered that mice genetically altered to lack a molecule known as the EP3 receptor tend to be more active during their normal sleep cycle and to eat more. In the study, this led to weight increases of up to 30 percent relative to mice with the receptors.

The EP3 receptor is one of four types of receptors for prostaglandin E2 (PGE2), the most important inflammatory mediator that controls a variety of physiological functions including fever, fertility, and blood pressure. The most common anti-inflammatory and analgesic treatments like ibuprofen are aimed at reducing PGE2 signaling at all four prostaglandin receptors.

The absence of EP3 receptors has long been known to prevent fever response in mice, and it was this effect that the Scripps Research team was originally studying. Previous research on mice lacking the receptors had focused on fever inhibition until mice were about three months old. The team wanted to better understand the process by studying if fever inhibition continued later in life.

When the mice were four to five months old, the researchers made a startling discovery. The older mice still did not develop fever, but the researchers noticed that these mice were gaining weight.

"The experimental mice were clearly getting heavier than their wild type litter mates, the control mice," says Sanchez-Alavez. "We realized there was something interesting going on with these animals, so we started watching their behavior at night and during the day."

During continuous monitoring of temperature and motor activity, the researchers realized that the mice without the EP3 receptors were more active during the light hours-the nocturnal mice's "night"-and, more importantly, were eating during this time. The increased activity led to higher body temperatures, but this did not burn enough extra calories to balance the additional e
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Source:Scripps Research Institute


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