Snack Attack Gene Link

Another piece falls into place to explain expanding waistlines, reports Roger Highfield

A gene that plays a role in inflammation and fever has been found to regulate body weight too, by curbing our urge to snack at night.

When the gene is turned off, activity during the hours of sleep goes up, along with the drive to eat, a discovery that suggests a new way to tackle obesity.

The gene is the code for a protein switch that could, at the very least, help scientists to better understand obesity and its link with inflammation. However, if it can be flicked on by a drug, it could lead to new treatments to prevent the western world's ever expanding waistlines.

Researchers from The Scripps Research Institute in La Jolla, California, report the findings in the Proceedings of the National Academy of Sciences, which link the protein to getting up during sleep ours for a bite to eat.

Led by neuroscientists Manuel Sanchez-Alavez and Prof Tamas Bartfai, the team discovered that mice genetically altered to lack a protein known as the EP3 receptor tend to be more active and to eat more, causing weight increases of up to 30 percent relative to mice with the protein.

The EP3 receptor is one of four types molecular switches that respond to a type of hormone, called prostaglandin E2 (PGE2). The switch plays a role in inflammation, fever, fertility, and blood pressure. Scientists already know that it is possible to play with these switches because the drug ibuprofen givens pain relief this way.

The Scripps team was investigating the role of EP3 in inflammation and were studying mice that lack the protein and do not develop fevers. 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 a significant amount of weight.

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

During continuous monitoring of body temperature and activity, the researchers realised that the mice without the EP3 protein were more active during the light hours - the "night" for mice, which are nocturnal creatures, and, more importantly, were eating during this time.

The increased activity led to higher body temperatures, and thus more energy expenditure, but this did not burn enough extra calories to balance the additional amount they ate compared with normal mice, so the mice weighed 15 to 30 percent more than control mice. The next step will be to pinpoint which part of the body the protein has most effect on, to pinpoint the link between this gene and waistlines.

Prof Bartfai notes that inflammation seems to be linked to obesity and metabolic syndrome - a blend of obesity, high cholesterol and blood pressure and diabetes. The mice "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.

This could lead to the development of treatments that could prevent or reverse these conditions, he concludes.

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