Overweight? It May Just Be Body Chemistry

Newswise — 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.

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 http://www.foodandfitnessadvisor.com.)

“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.”

Munchie receptors

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 weight gain.

“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 receptors
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 diabetes.

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 Library.

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 placebo.

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 overeating:

• 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 portion sizes.

• 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 promote overeating.

• Eat slowly; it takes the brain 20 minutes to sense that you’re full.

• Don’t do other activities while you eat, such as watching TV.