29 July 2010

Resveratrol blocks weight gain in primate study

Gray mouse lemur
Resveratrol—a natural red-wine compound previously shown to protect mice against excess weight gain when fed a high-fat diet—has now been found to reduce seasonal weight gain in gray mouse lemurs in a primate model of obesity.

The study was published in BMC Physiology by a team of researchers from the Centre Nationale de la Recherche Scientifique, Museum National d’Histoire Naturelle, of Paris, who wrote that they had “demonstrated for the first time the short-term effects of resveratrol on the metabolism of an heterothermic [with varying body temperatures] primate.”

Gray mouse lemurs are a species of prosimian primate that can double in weight (seasonal fattening) within a matter of weeks. This increase in energy reserves is induced by the arrival of shorter days and longer nights (shorter photoperiod), which serves as a means of adapting to the long dry winters in its natural environment in Madagascar.

When given four weeks of resveratrol supplementation at the time of pre-winter fattening (200 milligrams per kilogram per day), the gray mouse lemurs exhibited the following “significant effects on energy metabolism”:

Reduction in seasonal body-mass gain associated with an increase in resting metabolic rate of 29 percent while decreasing food calorie intake by 13 percent.

Strong reduction of daily heterothermia expression (changes of body temperature relating to season) with no change in the daily amount of locomotor activity.

An increased secretion of glucose-dependent insulinotropic polypeptide (a gut hormone known to induce insulin secretion) levels that may play an additive role in limiting body-mass gain.

The researchers concluded that, “resveratrol activates energy expenditure by inducing an increase in resting metabolic rate and a decrease in torpor [temporary hibernation] patterns that play key roles in energy saving in this primate. Moreover, resveratrol had a satiety effect in this primate that reduced their spontaneous food intake.”

Resveratrol’s effects are potentially due to stimulation of SIRT1, one of family of sirtuin enzymes, that has a direct role in fat metabolism. Calorie restriction and, recently, intermittent fasting have also been shown to activate SIRT1 activity.

Mouse Lemurs to Humans

In a prepared statement, Fabienne Aujard, a co-author of the study, wrote, “The physiological benefits of resveratrol are currently under intensive investigation, with recent work suggesting that it could be a good candidate for the development of obesity therapies.”

When asked through e-mail about how the study related to humans, Aujard replied that the main point of the study is that the gray mouse lemur is a non-human primate, “This species is genetically closer to human. The data obtained with this lemur should be more easily extrapolated to humans compared to rodent studies.”

Investigation conducted in humans have mainly studied bioavailability in lesser amounts, not in the high amounts given to the lemurs (equivalent of a human weighing 70 kilograms taking 14 grams of resveratrol). At present, the maximum single dose studied in humans has been 5 grams (70 milligrams per kilogram for a human of 70 kilograms).

“However, despite being a primate, the mouse lemur’s organism is certainly very different from that of a human because of its size and its seasonality,” writes Aujard. “The mouse lemur is a small animal and, like all small mammals, it has a very active metabolism, thus, a very important nutrient metabolism. Therefore, we believe that the doses to be ingested by human to reach the same long-term effects will certainly be lower than that given to lemurs.”

The general recommendation for humans is between 50 to 500 milligrams daily, which is safe as supported by human clinical studies. Although this study shows promising results, it is not yet known whether or not resveratrol will influence fat metabolism or body composition in humans.

Source: Dal-Pan A, Blanc S, Aujard F. Resveratrol suppresses body mass gain in a seasonal non-human primate model of obesity. BMC Physiol 2010;10:11.

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