Fructose Sets Table For Weight Gain
ScienceDaily (Oct. 19, 2008) — Eating too much fructose can induce
leptin resistance, a condition that can easily lead to becoming
overweight when combined with a high-fat, high-calorie diet, according
to a new study with rats.
Although previous studies have shown that being leptin resistant can
lead to rapid weight gain on a high-fat, high-calorie diet, this is the
first study to show that leptin resistance can develop as a result of
high fructose consumption. The study also showed for the first time
that leptin resistance can develop silently, that is, with little
indication that it is happening.
The study, “Fructose-induced leptin resistance exacerbates weight gain
in response to subsequent high-fat feeding,” was carried out by
Alexandra Shapiro, Wei Mu, Carlos Roncal, Kit-Yan Cheng, Richard J.
Johnson and Philip J. Scarpace, all at the University of Florida
College of Medicine in Gainesville. The study appears in the American
Journal of Physiology – Regulatory, Integrative and Comparative
Physiology, published by The American Physiological Society.
Leptin as regulator
Leptin is a hormone that plays a role in helping the body to balance
food intake with energy expenditure. When leptin isn’t working -- that
is, when the body no longer responds to the leptin it produces -- it’s
called leptin resistance. Leptin resistance is associated with weight
gain and obesity in the face of a high-fat, high-calorie diet.
Obesity has been a growing problem in the U.S. and in other parts of
the world and fructose has been suspected of playing a role. Fructose
is the sugar found in fruit, but it’s not the normal consumption of
fruit that is the problem. Table sugar and high-fructose corn syrup are
about 50% fructose and these ingredients have become increasingly
common in many foods and beverages. With sugar and high-fructose corn
syrup being added to many foods, people now eat much more fructose than
The University of Florida researchers hypothesized that a high-fructose
diet could lead to leptin resistance, which in turn could lead to
exacerbated weight gain in the face of a high-fat, high-calorie diet, a
typical diet in industrialized countries. To test their hypothesis, the
research team performed a study with two groups of rats. They fed both
groups the same diet, with one important exception: one group consumed
a lot of fructose while the other received no fructose.
Two groups similar over six months
During these six months, there were no differences in food intake, body
weight, and body fat between rats on the high-fructose and the rats on
the fructose-free diets. In addition, there was no difference between
the two groups in the levels of leptin, glucose, cholesterol or insulin
found in their blood. There was only one difference at the end of the
six months: The rats on the high-fructose diet had higher levels of
triglycerides in their blood.
The researchers next tested the animals to see if they were leptin
resistant. They injected all the animals with leptin, to see if they
would respond by eating less. Animals whose leptin response is
functioning normally will lower their food intake. The researchers
discovered that the rats on the high-fructose diet were leptin
resistant, that is, they did not lower their food intake when given
leptin. The no-fructose animals responded normally to leptin by eating
This first six months of the study showed that leptin resistance can
develop silently. “Usually, leptin resistance is associated with
obesity, but in this case, leptin resistance developed without
obesity,” Shapiro said. “This was very surprising.”
Role of diet
Having seen that leptin resistance could develop silently, the
researchers next wanted to find out what would happen if they switched
the rats to a high-fat, high-calorie diet -- the kind many Americans
eat. They found that the animals exposed to the high-fructose diet, the
leptin resistant rats, ate more and gained much more weight and fat
than the leptin responsive animals on the fructose-free diet. All told,
this study showed that leptin resistance can:
- develop by eating a lot of fructose
- develop silently, that is, with
very little indication it is happening
- result in weight gain when
paired with a high fat, calorie dense diet
Scarpace said the study
suggests it is the interaction between consumption of large amounts of
fructose-containing foods and eating a high-fat, high-calorie diet that
produces the weight gain. “This study may explain how the global
increase in fructose consumption is related to the current obesity
epidemic,” Shapiro said.
How it happens
Other studies have shown that elevated triglycerides impair the
transport of leptin across the blood brain barrier. The researchers
hypothesize that the elevation in triglycerides produced by fructose
prevented leptin from reaching the brain. If leptin does not reach the
brain, the brain will not send out the signal to stop eating.
“The presence of high fructose alters the way leptin works, fooling the
brain so that it ignores leptin,” Scarpace said. Consumers should be
cautious about what they eat, checking labels to see how much sugar the
items contain, Shapiro said.
The researchers hope to perform future studies to find out if leptin
resistance can be reversed by removing or reducing the fructose content
of the diet.
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