A molecule derived from the wine against obesity

Occurring naturally in red wine but also in more than 70 plants including grapes, peanuts or cocoa, resveratrol never ceases to amaze and excite researchers.

For twenty years, this molecule that belongs to the family of polyphenols has been the subject of more than 3300 scientific publications. First of all, for its anti-oxidant protection against cardiovascular disease and cancer.

Resveratrol provided by regular consumption of wine would be a biological explanation to the French Paradox, this apparent contradiction between a low cardiovascular mortality and a diet high in fat and sauces.

Other studies have also highlighted the benefits of longevity, neurodegenerative disorders, diabetes, obesity... Common to polyphenols, these effects would be strong with resveratrol.

The latest study, published this week in the journal Physiology, provides new data in primates showing that supplementation with resveratrol significantly reduced weight gain during winter by higher energy costs and an appetite suppressant.

So far, most work with resveratrol had focused on rodents made obese by genetic manipulation or high-calorie diet. The team of Fabienne Aujard (CNRS, National Museum of Natural History, Brunoy) chose to study lemurs, small primates from a hundred grams whose physiology is very special.

These lemurs have a marked seasonal rhythm, they almost doubled their weight in winter thanks to a progressive storage of fat. They are also heterothermal, in other words, their internal temperature may fall sharply, which is a source of energy conservation.

On the longevity of eight to ten years, the animals are a model increasingly used by researchers to study aging, especially the brain. Producing results for four weeks, the season when they naturally tend to store fat for winter, six lemurs have been subjected to a diet rich in Resveratrol 200 mg/kg day dose a priori well beyond what would normally consume a human.

Their weight, body temperature, energy expenditure and intake were carefully monitored. The results are very conclusive. "Weight gain, usually a gram per day at this period has been divided by five," said Fabienne Aujard. A slightly positive balance reflecting a net increase in energy expenditure (up 29% of resting metabolism in particular) and reduced calorie intake (13% from the third week.)

Researchers have also found smaller variations of body temperature of lemurs, without reducing their physical activity, then they are usually prone to lethargy. "We expected the increased energy expenditure, which has already been described in mice. What surprised us is the effect on satiety, appetite suppressants such, it was not known , "says Fabienne Aujard.

The work of researchers Brunoy is far from complete. With these primates, they study the long-term effects of resveratrol on age-related diseases and longevity of these animals.

"These results are interesting, especially the appetite suppressant effect, but we must know whether it exists with physiological doses of resveratrol," says Professor Norbert Latruffe who is working on mechanisms of action of this intimate polyphenol, especially in the field of inflammation and carcinogenesis.

Prof. Johan Auwerx of the Ecole Polytechnique Federale de Lausanne, also welcomed the work on a primate model. "This is a step closer to the man," he says. A few years ago, this researcher had established that the antiobesity and antidiabetic properties of resveratrol are related to the activation of an enzyme (sirt1) family of sirtuins. In fact, resveratrol works by stimulating the mitochondria (energy center of the cell), then the body begins to burn its reserves.

After this discovery, Professor Auwerx identified a synthetic molecule, TRS 1720 kind of super-resveratrol, the results have been spectacular in mice. Sirtuin activators now being tested in humans with several disorders including diabetes and cardiovascular disease. Rather than therapeutic molecules, Dr. Auwerx is now seeking to develop a nutritional supplement containing resveratrol. But it is still far from being ready. "The final composition is not fixed yet. And with the new European regulations on nutraceuticals, development is going to be almost as long as that of a drug", says the researcher.

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