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Nervy approach to fighting fat

Disrupting the vagus nerve, which runs between gut and brain, could become a kinder obesity surgery.

June 09, 2008|Chandra Shekhar | Special to The Times

Weight loss surgery works, but is so invasive and has such unpleasant long-term side effects that it's recommended for only a fraction of the obese population, and even many in that group are reluctant to undergo the surgery. In hunting for a simpler and safer alternative, researchers have zeroed in on a nerve that carries much of the communication between brain and gut.

Disrupting this communication, they believe, could lead to safe, effective and sustained weight loss -- mainly by cutting off signals from the gut that tell the brain it's time to eat. The concept still has to be validated, says Dr. Philip Schauer, immediate past president of the American Society for Metabolic and Bariatric Surgery, a Gainesville, Fla.-based association of U.S. weight loss surgeons, "But if it gives even a modest amount of weight loss, it could be a winner."

Two different methods of disrupting the vagus nerve are now in clinical trials. One method, vagotomy, simply cuts the nerve and permanently disables it. The other, vagal nerve blocking, uses an electric current to periodically confuse the nerve and prevent it from transmitting signals. Preliminary results suggest that both methods help to safely reduce excess body weight by about 20% on average within six months of therapy.

Amid the complex set of muscles, nerves and organs that team up to regulate body weight, one anatomical feature stands out: the vagus nerve. Running from the brain through the esophagus and branching out to reach nearly every part of the digestive system, this nerve plays a key role in weight gain.

When the stomach is empty, the vagus nerve informs the brain and triggers the feeling of hunger. When the stomach contains food, the vagus tells the brain and relays back the brain's commands to secrete stomach acid to help digest the food. The brain's control of the passage of food through the digestive system also relies on the vagus nerve. In short, without the vagus, we would get less hungry, and food would stay longer in the stomach.

The vagus nerve does even more than that. While food is being digested, the brain tells the pancreas to make insulin, a hormone that helps store energy from food in fat tissues. That command passes through the vagus nerve. So too does another that instructs fat tissues to grow by absorbing more nutrients. "Everything this nerve does is designed to make you take up energy and put it into your fat," says Dr. Robert Lustig, a pediatric endocrinologist at UC San Francisco and one of the lead investigators in a 30-patient clinical trial of vagotomy for weight loss. "It's your energy storage nerve."

First noticed in the 1940s

The vagus nerve's pivotal role in weight gain would appear to make it a prime target of obesity therapy. But this potential was discovered almost by accident in the 1940s, when surgeons treating intractable ulcers tried vagotomy to help reduce stomach acidity. The method worked, and soon became widely used (drug therapy eventually superseded it). But the operation had an unexpected side effect: It made obese patients lose weight.

Early vagotomy surgeries cut the entire vagus nerve as well as some stomach muscles. This drastic method caused undigested food to be dumped into the intestines, leading to a range of unpleasant side effects, such as diarrhea, vomiting, flushing and dizziness.

The modern form of the procedure is much more refined: It cuts only the parts of the vagus that control hunger and weight gain, leaving the stomach muscles and the rest of the nerve intact. As a result, the side effects of vagotomy are now much milder and tend to disappear after a few months, Lustig says.

Launched in 2005, the trial Lustig is involved in is taking place at UC San Francisco and the University of Rochester. About 80% of the 30 subjects in the trial lost an average of about 30% of their excess body weight in the first six months, Lustig says. The trial is sponsored by EndoVx, a Napa-based company that is developing a device to simplify the vagotomy procedure.

One of Lustig's patients, 57-year-old Garth Michaels of Walnut Creek, says he lost about 40 pounds within months of surgery. He got rid of 60 pounds more over the next year after starting a regular exercise program, and is down to a manageable 220 pounds.

"It's harder for extra weight to come on to me, and it's easier for it to fall off than it used to be," he says. In fact, he adds, he feels that his whole attitude toward food has changed for the better after his vagotomy. "I eat less food, eat it more slowly and enjoy it more."

Once the vagus nerve is cut, it can't be restored -- a potential drawback, because the reduced appetite and slowed digestion may no longer be required or even desirable once a patient attains a healthy body weight. And so some researchers are testing whether it's possible to achieve the weight loss effects of vagotomy while keeping the vagus nerve intact.

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