Could nerve-snip spur weight loss

WASHINGTON (AP) -- An old ulcer operation is getting new attention as a possible alternative obesity surgery: a quick snip of a nerve that helps control hunger.

It's far from clear whether cutting the vagus nerve really helps -- initial pilot studies in a few dozen patients have just begun. Skeptics abound, and even proponents say it wouldn't lead to nearly as much weight loss as more traumatic operations that shrink the stomach and reroute intestines.
It's part of a hunt for middle-ground options for people scared of today's surgery, or those not quite fat enough to qualify for it.
"By no means do I think this is a panacea," cautions Dr. Robert Lustig of the University of California, San Francisco, who, along with University of Rochester surgeons, is studying the method.
"But I think this will be a rational alternative for a cadre of patients that are sort of in the middle there. With as much obesity as we have in this country, that's a big middle."
More than 177,000 people underwent obesity surgery last year, according to the American Society for Metabolic and Bariatric Surgery. The most popular method is gastric bypass, stapling the stomach to create a tiny pouch. Options include placing an adjustable band around the stomach, or cutting off the stomach's side and rerouting the intestines.
Surgery can produce life-altering weight loss, if recipients adhere to diet and exercise advice, but each method comes with varying degrees of pain and risk, including a rare chance of death. So doctors are searching for alternatives.
Enter the vagus nerve, which snakes from the brain to the abdomen, with fibers reaching into multiple organs with different effects. Among them: The nerve spurs gastric acid production, and in the 1970s, surgery to cut where it attaches to the front and back of the stomach brought ulcer sufferers great relief -- after they recovered from open-abdominal surgery. Once better acid-reducing medications came along, this arduous operation was abandoned.

Yet surgeons at the time noticed, and subsequent animal studies confirmed, that these vagotomies could trigger weight loss. In addition to a less acidic stomach's slower digestion, the vagus helps control appetite-stimulating brain hormones and signals our bodies to store more fat, Lustig explains.
Since doctors today can snip the nerve far less invasively, through just five pencil-sized cuts in the abdomen, it was time to test in the obese.
Thirty patients had a vagus snip at UCSF or the University of Rochester. The study isn't complete. But of the 11 who are a year past surgery, all but one are shedding pounds, losing an average of 18 percent of excess weight so far, Lustig and Rochester's Dr. Thad Boss reported at last month's bariatric society meeting.
They suffered no serious side effects, and went home hours later with little pain.
"Every patient who had the vagus nerve cut says they're not hungry," adds Lustig -- although the one who didn't respond got hungry again six weeks after surgery, perhaps because the nerve healed.
That's less than half the weight loss of standard surgeries, warns Dr. Neil Hutcher of Bon Secour St. Mary's Hospital in Richmond, Virginia, and a past president of the bariatric society.
"I have my doubts that vagotomy alone is going to be a significant weapon," says Hutcher, who often cuts the nerve during standard gastric bypasses for a different reason -- to help those patients avoid the side effect of heartburn-causing acid buildup.
But, when Greensboro, North Carolina, surgeons added a vagotomy to 25 patients getting bands on their stomachs, the nerve-snip seemed to make that usually more modest operation about as effective as a gastric bypass -- with 43 percent loss of excess weight at six months, and counting.
Other doctors are testing whether implants that treat epilepsy by stimulating the vagus nerve also might trigger weight loss, with mixed results so far.
For now, Boss stresses that vagus nerve-snipping remains highly experimental. He and Lustig will track their 30 patients for 18 months to check if ultimate weight loss is enough to warrant further study, and who responds best.
The goal is to help people like Garth Michaels of Walnut Creek, California, who twice backed out of standard obesity surgery, fearful of side effects and a long recovery. Thirteen months after he volunteered for the vagotomy experiment, he has dropped 66 pounds, to 246.
That's a much more gradual loss than with regular surgery, but Michaels says having his hunger curbed help him finally learn to exercise. He spends a half-hour on an exercise bike most days. And he learned to avoid former diet saboteurs -- french fries, sweets -- that caused foul burping after his vagotomy, in favor of fruits and vegetables.
"I will lose more, there's no doubt about it," says Michaels, 56, whose goal is 175 pounds. "It has given me such hope. >>>Cnn

Cellular message movement captured on video

These time-lapse images of a bovine aortic endothelial cell reveal the motion toward the cell's nucleus of a message-carrying protein called paxillin (orange) in tandem with actin filaments (green). Credit: UC San Diego

Proper signaling step required for controlled cell growth -- otherwise, cancer and other diseases can result
Scientists have captured on video the intracellular version of a postal delivery service. Reporting in the journal Biochemical and Biophysical Research Communications (BBRC), bioengineering researchers at UC San Diego published videos of a key message-carrying protein called paxillin moving abruptly from hubs of communication and transportation activity on the cell surface toward the nucleus. Paxillin was labeled with a red fluorescence marker to make it stand out in live cells.

“It’s amazing to us. We thought the cell was so simple,” said Shu Chien, the senior author of the BBRC paper and a professor of bioengineering at UCSD’s Jacobs School of Engineering. “But it’s really very complex and I’m not sure we’re covering much as yet. We certainly don’t know all the interactions among these molecules that bring the cell into action.”

Cancer researchers are eager to understand paxillin’s many interactions because their malfunctions have been linked to a variety of cancers, tumor metastasis, and other disease processes. Tumor-causing versions of signaling molecules may attach to paxillin and disturb the normal adhesion and growth factor signaling steps required for controlled proliferation and cell growth. For example, human papilloma virus, which can cause cervical cancer, makes a protein that binds to paxillin and that interaction may contribute to the carcinogenic potential of the sexually transmitted virus.

Chien and Hu obtained cells for their most recent study from the inner membranous lining of a cow aorta. They added genetically engineered proteins tagged with red and green fluorescence markers to the bovine aortic endothelial cells, grew them in tissue culture, and filmed them while they passed fluid across the cells’ surface in a simulation of flowing blood. With that physical stimulus, paxillin consistently moved in the same direction as the fluid flow.

Paxillin is found primarily at focal adhesions, busy intersections of activity scattered around the cell’s cytoplasmic membrane. Focal adhesions are regions rich with receptors for growth factors and they are also structural attachment points that link the extracellular world to the protein filaments and tubes that comprise a cell’s internal cytoskeleton.

While researchers showed that paxillin serves as a docking station for a variety of signaling and structural proteins, they have been limited to visualizing paxillin with dyes that stain cells rigidly attached to microscope slides. Those snapshots of fixed cells can’t reveal paxillin movement.

“We can now see the dynamics of how paxillin and other proteins move inside the cell with new fluorescent labels and live-cell video microscopy,” said Chien, director of the Whitaker Institute of Biomedical Engineering at the Jacobs School.

The two-color labeling technique of Chien and Hu revealed that red-labeled paxillin is linked to green-labeled actin filaments, the thinnest of three types of protein filaments that make up the cytoskeleton of cells of higher organisms. Paxillin either slides along the actin filaments or is pulled by them. In a surprise, Chien and Hu also showed that paxillin itself forms long, fibrous structures in the cell cytoplasm.When actin is chemically removed, paxillin no longer moves and its fibrous structures disappear.

“As least by showing that paxillin and actin filaments move together we have some insight into the possibility of how paxillin can transmit information from one region of the cell, such as the periphery, to another region of the cell, such as the nucleus,” said Chien. “The whole situation is much more complex than we have been able to show.”

Chien, Hu, and their colleagues at UCSD had previously reported that paxillin can be rapidly assembled and disassembled, and they hypothesize that this process enables cell migration by assembling new focal adhesion sites in the direction of cell movement and disassembling them on the trailing side of the cell. Researchers are applying the fluorescence-labeling technique to the many other signaling and structural proteins found predominantly at focal adhesions.

“When we piece all of these things together we can get a more complete understanding of how the cell functions, both in migration and signal transduction,” said Chien. “If we can understand the details of these processes, we can not only understand how normal cells function, but we can also look at diseased cells to see why they sometimes don’t move properly or why they don’t transmit information properly.”