By Nathan Seppa
Resveratrol, the chemical in red grape skins that seems to underlie the healthful effects of red wine, limits the number of fat cells that can develop from stem cells, a new study finds.
The finding, combined with resveratrol’s other beneficial effects at the cellular level, might explain in part the French paradox, said study coauthor Martin Wabitsch, a pediatric endocrinologist at the University of Ulm in Germany, who presented the work Monday in San Francisco during a meeting of the Endocrine Society. The paradox refers to the observation that people in France seem to have a low incidence of coronary heart disease and seem to stay thin despite a diet high in fats.
Scientists formerly believed that people have a set number of fat cells at birth, but now widely understand that stem cells can differentiate into full-fledged fat cells well into adulthood and old age.
In the new study, laboratory tests on human cells showed that resveratrol inhibits the number of nascent fat cells that grow into mature fat cells, Wabitsch said. This could limit the addition of fatty tissue in the body, he hypothesizes. If fats and carbohydrates from food cannot be larded into fat cells, they are typically broken down and burned as energy instead, he says.
Thus, fat deposition might not depend solely on the amount of energy consumed, he says. With resveratrol, he said, “It might be metabolized more actively instead of stored.”
Bolstering that assertion, Wabitsch and his colleagues also showed that resveratrol lowers the cells’ production of interleukin-6 and -8, two inflammatory proteins that are elevated in obese people and may contribute to fat accumulation.
What’s more, in these tests resveratrol also induced mature fat cells to maintain healthy amounts of a valuable compound called adiponectin, which earlier research suggested can protect against diabetes.
In addition to showing up in red grape skins, resveratrol occurs in Japanese knotweed. Earlier laboratory and animal tests suggested that resveratrol may fight aging, cancer, inflammation and atherosclerosis. But scientists have not yet reported test results for resveratrol in people.
Resveratrol’s mechanism of action is not entirely clear, but the compound seems to activate at least one member of a family of proteins called sirtuins. While also poorly understood, some sirtuins show up in fat cells.
Previous work showed that low levels of sirtuins allowed fat cells to add fats and to proliferate freely from nascent to mature stages, a recipe for weight gain. Conversely, that work also showed that an increase in sirtuins — in that case the compound Sirt2 — kept stem cells from maturing into full-fledged fat cells and inhibited mature fat cells from filling with fats.
In the new study, resveratrol’s good effects failed to emerge in either nascent or mature fat cells engineered to lack a sirtuin called Sirt1, Wabitsch said.
As potential therapeutics, “the sirtuins are a new class in the armamentarium of diabetes and pre-diabetes management,” says Henry Anhalt, a pediatric endocrinologist at Animas Corp. in West Chester, Pa., who wasn’t involved in this study. Sirtuins seem to curb the risk of obesity, cardiovascular disease and inflammation, all of which have been correlated with development of diabetes and its complications. The finding that resveratrol seems to work through a sirtuin (Sirt1) opens up new research opportunities, he says.
But Anhalt notes that the quantities of resveratrol used in these and other tests have been large, far more than the amounts delivered to a cell in a person who just drank a glass or two of pinot noir. Being able to produce resveratrol in a capsule or pill and not having to drink excess amount of wine to get enough “would be a tremendous advance,” if it indeed proves therapeutic, he says.
Resveratrol has shown considerable potential since it was discovered in the 1990s, with particular attention paid to its anticancer effects. The compound seems to fight cancer by inducing malignant cells to undergo a form of programmed cell suicide called apoptosis. In contrast, resveratrol thwarts fat cell proliferation by keeping nascent cells from developing into mature fat cells, Wabitsch said.
