Fighting Fat

CURE, Fall 2005, Volume 4, Issue 3

Discovered in 1994, scientists heralded leptin as a potential cure to obesity. Researchers believed that if they harnessed the power of leptin, they could trick the body into believing it wasn’t losing weight. Cravings would go down, calories would be burned and weight would be lost. Unfortunately, it didn’t prove that easy.

Even today only Meridia (sibutramine) and Xenical (orlistat) have been approved for long-term weight loss. In clinical studies, along with diet and exercise, both drugs helped people lose 5 to 10 percent of their body weight and keep it off longer than diet and exercise alone.

Meridia prolongs the effect of the hormone serotonin, which is released after eating. Serotonin signals to the brain that the body is full and doesn’t need additional food. Common side effects of Meridia include insomnia, headache, dry mouth and constipation. Xenical, on the other hand, allows the body to absorb only 60 percent of dietary fat. Because a third of consumed fat is not absorbed, it can cause diarrhea, flatulence and bloating, especially after a high-fat meal. Xenical must be taken with a vitamin supplement to help the body absorb certain nutrients.

Acomplia (rimonabant) is the first in a class of drugs that act to block the brain’s endocannabinoid system, thought to be a central control for the body’s cravings, such as for food and nicotine. While marijuana stimulates the cannabinoid receptors in the brain, the body also produces cannabinoids. Acomplia acts against this mechanism by blocking the cannabinoid receptors in the brain, reducing the craving for food. What makes Acomplia so extraordinary is that it acts against two pathways. By also blocking the cannabinoid receptor found in fat cells, triglyceride levels decrease and good cholesterol levels increase, producing weight loss.

A recent Acomplia trial showed participants lost an average of 20 pounds, or about 10 percent of their body weight, while on the drug for one year. Yvette Cardozo participated in the trial, losing 30 pounds on the drug in addition to diet and exercise. “Acomplia is the only thing that has ever worked for me,” she says. “It made me normal.” But she adds that after the study ended, she began gaining the weight back. The Food and Drug Administration is expected to approve Acomplia next year.

Most drug treatments, including many others in development, only produce modest weight loss, usually no more than 10 percent of total body weight. But complemented with diet and exercise these medicines could lower the risk of many obesity-related diseases.

Another option being studied at M. D. Anderson Cancer Center works by directly targeting fat cells. Researchers are studying whether starving individual fat cells by attacking the proteins in blood vessels that feed fat cells will help people lose weight. The procedure, called molecular liposuction, reduced body fat in mice by 30 percent and quickly improved their overall health. Preclinical research is ongoing.

Weight loss surgery, such as gastric bypass, has shown the most success in regards to the amount of weight lost and maintenance. It is usually only available for people with a BMI over 40 and comes with possible surgical complications, ulcers and a lifetime restrictive diet, including nutritional supplements. With any weight loss intervention, a healthy diet and increased exercise are needed to achieve the full benefit.