Two different chemicals produced naturally by the body could be used in the future to stem the dangerous rise in obesity, according to new studies out today.
UK researchers writing in today's issue of the New England Journal of Medicine suggest that supplementing the gut hormone PYY3-36 could reduce people's appetite, helping them to lose weight.
The team from Imperial College London and Hammersmith Hospital have discovered that obese people have lower than average levels of the hunger-regulating hormone PYY3-36. They report that infusions of PYY3-36 reduced the perceived appetite and calorific consumption of both lean andoverweight volunteers by around a third for a period of 24 hours.
PYY3-36 is released from the gut in response to eating, signalling to the brain that a meal has been eaten. Obese people have on average, 30 per cent less PYY3-36 than lean volunteers.
Author Professor Steve Bloom from Imperial College London and the Hammersmith Hospital, said: "Our previous research has shown that it is possible to reduce calorific consumption in lean volunteers by giving PYY3-36. These new findings suggest boosting PYY3-36 offers a novel approach towards treating the epidemic of obesity in our society."
Co-author Dr Rachel Batterham, now based at University College London, explained: "Further research is now needed to establish whether we can change people's diet to increase the release of this hormone."
The researchers studied 12 obese and 12 lean volunteers in a double-blind, placebo controlled crossover study. After an overnight fast, subjects were given a 90 minute infusion (placed on an intravenous drip) of either PYY3-36 or placebo (a saline solution). Two hours after the end of the infusion, the volunteers were offered an unlimited buffet meal.
All 24 volunteers ate less on the day when they received a PYY3-36 infusion compared with the placebo day. Overall PYY3-36 reduced calorific intake by a third in both the lean and obese subjects.
A second study out today by US researchers reveals that a natural fat compound, the fatty acid oleylethanolamide (OEA), has a similar effect on hunger.
A team from the University of California Irvine College of Medicine report in today's Nature that the fat activates its cell receptor molecules to regulate hunger and metabolism. They found that by increasing OEA levels while maintaining normal levels of these cell receptors, they could reduce appetite and weight in rodents, as well as lower their blood cholesterol and triglyceride levels.
Daniele Piomelli, professor of psychiatry and pharmacology, said: "In earlier studies, we found that OEA can be an important regulator of eating behaviour, but we didn't know how it worked. We were excited to find that OEA activates cell receptors that have already been the focus of successful drug development. This gives us hope for a new class of anti-obesity drugs based on natural chemicals."
To test the role of OEA and its receptors, Piomelli's team fed a high-fat diet to two groups of mice - one of regular mice, the other a mutant group with its OEA cell receptors genetically removed. After the mice became obese, they were treated with OEA for four weeks. Normal mice ate less and lost weight, while OEA had no effect on the group that lacked the cell receptors, suggesting that OEA only can reverse weight gain when active cell receptors are in place.
They also found that in normal mice, OEA lowered blood cholesterol and triglyceride levels by reducing levels of hunger-inducing nitric-oxide molecules. These reductions were not seen in the mutant mice group.
"This shows the receptors are not only necessary for the hunger-curbing and weight-reducing actions of OEA, but may contribute to the overall stability and maintenance of our feeding system," Piomelli said.
Both these compounds are likely to gain significant attention owing to the fact that they are naturally produced in the body and therefore could be safer than current drugs as long-term obesity treatments.
"There are many drugs being tested for obesity in current clinical trials, but most don't succeed because they are not well tolerated by patients. As an endogenous compound, OEA has the potential for being much less toxic than other man-made compounds," explained Piomelli.
The numbers of obese people is rising dramatically in the developed nations, particularly in the UK and US. Nearly 30 per cent of Americans are obese, according to the Centers for Disease Control, and occurrence of obesity has risen by almost 60 per cent since 1991.