Overweight? It May Just Be Body Chemistry
— Ever had the munchies even after you just ate? That urge
to snack may be due to an overactive chemical “feedback”
system that regulates appetite, food intake, fat metabolism,
and body weight. The chemical culprit is called the
endocannabinoid (EC) system, and it’s the latest target in
medicine’s battle of the bulge. We can’t change the EC
system, but we may be able to work around it by redirecting
the cues that make us overeat.
(1) High-fat, high-carb food activates
cannabinoid receptors in the brain, (2) increasing
endocannabinoids and boosting appetite. (3) Increased
food intake boosts fat storage and insulin resistance,
leading to weight gain. (4) Lack of satiety sends
signals to the brain to eat more.
The findings are in the February issue of Food and Fitness
Advisor, a monthly newsletter from Weill Medical College of
Cornell University. (For more information, click on
“What many people have traditionally viewed as a lack of
willpower could actually have a biochemical basis,” says
Louis J. Aronne, MD, director of the Comprehensive Weight
Control Program at New York Presbyterian Hospital-Weill
Cornell Medical Center. “It’s not just a matter of lack of
willpower to stop eating, or of an obesity drug not working,
but the body’s counterbalancing mechanisms that stops people
from losing weight.”
When your EC system is activated, it increases hunger and
decreases satiety, driving the desire for tasty food, says
Dr. Aronne. He calls this the “feed-forward” mechanism.
“When you eat a high-fat, high- carbohydrate food, it
activates the endocannabinoid system, leading you to eat
even more,” he explains. “The endocannabinoid system
interacts with other hormones to make you feel hungrier,
increases body fat, and drives weight gain. We now know that
the endocannabinoid system is overactive in obese people. In
one study, obese women were found to have higher levels of
endocannabinoids than lean women.”
Endocannabinoids are akin to the active chemical (cannabinoids)
in marijuana that triggers its effects, including the
“munchies.” There are cannabinoid receptors all over the
body—including the brain, the gastrointestinal tract, and
fat cells. When cannabinoid receptors are activated in the
brain (in the hypothalamus), it stimulates appetite, leading
to increased food intake, says Dr. Aronne.
In the gastrointestinal system, activated cannabinoid
receptors interact with insulin, the hormone that brings
energy from food into cells as glucose, to inhibit its
effects. An overactive EC system impairs the ability of
cells, especially muscle cells, to use insulin, leading to
insulin resistance, the precursor to type 2 diabetes.
Activating cannabinoid receptors in fat cells triggers
triglyceride production, increased fat accumulation, and
“It also appears that overactivating the EC system leads to
laying down of fat in the liver, which is a key factor in
insulin resistance,” says Dr. Aronne. “There is also data to
show that insulin and the hormone leptin, which are
important signals to the brain telling how much nutrition
has come in and how much fat is stored, also interact with
the EC system.”
Blocking cannabinoid receptors may dampen an overactive EC
system, reining in appetite, reducing weight, and improving
obesity-related risk factors for heart disease and type 2
A drug that blocks cannabinoid receptors, rimonabant (Acomplia),
is being considered by the U.S. Food and Drug Administration
(FDA) to treat people with type 2 diabetes. Four similar
drugs are also in the pipeline. “We’ve seen that blocking
these receptors results not only in reduction of food
intake, but also a reduction in triglycerides and glucose,
and even an increase in ‘good’ HDL cholesterol. And that’s
above and beyond any reduction in weight,” says Dr. Aronne.
A recent review of four placebo- controlled clinical trials
of rimonabant found it produces only moderate weight loss.
But even the average 5 percent weight loss seen in the
trials after one year of using 5 mg of rimonabant reduced
risk factors for type 2 diabetes and cardiovascular disease,
according to the October 17, 2006 edition of The Cochrane
A higher dose (20 mg) produced a larger weight loss, almost
11 pounds, as well as a reduction in waist circumference,
triglycerides, blood pressure, and raised low HDL
cholesterol. These are all risk factors for metabolic
syndrome, notes Dr. Aronne.
“In the clinical trial conducted in North America, there was
a 39 percent reduction in metabolic syndrome prevalence in
the rimonabant group versus 8 percent in the placebo group.”
However, the higher dose also produced more side effects
such as dizziness, nausea, headache, and depressed mood.
What can you do?
Aside from taking medication such as rimonabant to block EC
receptors, sibutramine (Meridia) to enhance satiety and
reduce appetite, or block fat absorption with orlistat (Xenical,
soon to be over the counter), you can’t really alter your
body chemistry, says Dr. Aronne. Both Meridia and Xenical
result in an average 6-10 pounds more weight loss than
However, you can use knowledge about the EC system to help
you work around it. For example, nutritionists have a number
of proven strategies that can help you defuse the urge to
snack or overeat, such as waiting 5-15 minutes for a craving
to pass, distracting yourself with other activities (such as
taking a walk), or even drinking a glass of water. If you’re
able to satisfy a craving with just a small portion of a
treat, then have it.
Choose foods that help increase your sense of fullness,
those high in water and rich in fiber, such as fruits and
vegetables; eating a piece of fruit can also help satisfy a
craving for sweets. Realize that it takes the brain 20
minutes to sense that you’re full. Slow down when you eat;
it promotes satiety and increases enjoyment.
A 2003 study suggests that exercise may activate cannabinoid
receptors, partly accounting for the “runners’ high” and for
increased appetite after a workout. So if you’re usually
ravenous after exercising, looking for low-cal ways to
satisfy your hunger can help you avoid taking in more
calories than you just worked off. Exercise also increases
the efficiency of insulin uptake in muscle cells—hampered
when the EC system is overactive.
Exercise is the key to maintaining weight loss, because it
counteracts the body’s natural tendency to use fewer
calories once you’ve lost weight, says Dr. Aronne.
“The body senses that less food is coming in, and its
response is to conserve calories. What it does is makes your
muscles more efficient, sort of like having a car that gets
better mileage as the gas gauge goes down. With a 10 percent
reduction in body weight there’s a 42 percent reduction in
energy expended during physical activity. Exercise blunts
that reduction in energy expenditure,” he explains.
In the end, “there’s no real shortcut to weight loss,”
concludes Dr. Aronne. “It amounts to taking in fewer
calories and burning off more.”
What you can do
To combat the “feed-forward” urge and stop mindless
Consume foods that are low in calories but high in fiber
and water to help make you feel fuller.
Use smaller plates and serving utensils to control
Beware of the “clean plate” mentality: visualize how
much you’re going to eat before you start eating.
Avoid all-you-can-eat restaurants and buffets; they
Eat slowly; it takes the brain 20 minutes to sense that
Don’t do other activities while you eat, such as