When we eat too much, obesity may
develop as a result of chronically high insulin levels, not the other way around.
That's according to new evidence in mice reported in the December 4th Cell
Metabolism, a Cell Press publication, which challenges the widespread view
that rising insulin is a secondary consequence of obesity and insulin
resistance.
The new study helps to solve this
chicken-or-the-egg dilemma by showing that animals with persistently lower
insulin stay trim even as they indulge themselves on a high-fat,
all-you-can-eat buffet. The findings come as some of the first direct evidence
in mammals that circulating insulin itself drives obesity, the researchers say.
The results are also consistent
with clinical studies showing that long-term insulin use by people with
diabetes tends to come with weight
gain, says James Johnson of the University of British Columbia.
"We are very inclined to
think of insulin as either good or bad, but it's neither," Johnson said.
"This doesn't mean anyone should stop taking insulin; there are nuances
and ranges at which insulin levels are optimal."
Johnson and his colleagues took
advantage of a genetic quirk in mice: that they have two insulin genes.
Insulin1 shows up primarily in the pancreas and insulin2 in the brain, in
addition to the pancreas. By
eliminating insulin2 altogether and varying the number of good copies of
insulin1, the researchers produced mice that varied only in their fasting blood
insulin levels. When presented with high-fat food, those with one copy and
lower fasting insulin were completely protected from obesity even without any loss of
appetite. They also enjoyed lower levels of inflammation and less fat in their
livers, too.
Those differences traced to a
"reprogramming" of the animals' fat tissue to burn and waste more
energy in the form of heat. In other words, the mice had white fat that looked
and acted more like the coveted, calorie-burning brown fat most familiar for
keeping babies warm.
Johnson says it isn't clear what
the findings might mean in the clinic just yet, noting that drugs designed to
block insulin have been shown to come with unwanted side effects. But, he
added, "there are ways to eat and diets that keep insulin levels lower or
that allow insulin levels to
return to a healthy baseline each day."
Unfortunately, constant snacking
is probably not the answer.
More information: Mehran et al.: "Hyperinsulinemia drives
diet-induced obesity independently of brain insulin production." Cell
Metabolism, DOI:
10.1016/j.cmet.2012.10.019
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