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.
Found in: Body & Brain and Genes & Cells
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