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Psychiatry Newsletter - Embraceable Roux

Hopkins BrainWise Spring 2011

Embraceable Roux

Date: March 30, 2011

A common surgery could clarify eating disorders while it mends obesity

Megan Dailey
With specific brain areas so difficult to target, neuroscientist Megan Dailey is investigating an intestinal route for eating-based problems.

The “Roux-en-Y” gastric bypass, the most common surgery for severely overweight adults, is a dramatic procedure—it disconnects a third of the digestive tract. But it’s also highly effective. Patients can shed roughly half of their life-threatening poundage. Type II diabetes can fade away.

Now the operation has been embraced by Hopkins researchers as a tool to clarify how the body regulates eating, says Megan Dailey with Psychiatry’s behavioral neuroscience lab. By adding to what’s already known of hunger and satiety, she explains, studies that mimic the gastric bypass might one day let surgeons retire it for something far simpler.

More than that, benefits could extend to psychiatry, says Dailey, a neuroscientist: “What we learn will go to increase understanding of eating disorders,” she says.  There’s a possibility of new classes of more finely targeted drugs to help counteract anorexia’s or bulimia’s physical effects.

But what about “the Roux” makes it a tool? “It’s that the operation sheds light on a hard-wired satiety mechanism in the small intestine,” Dailey explains. 

“Nobody has known exactly why the surgery causes weight loss,” she says. The fact that most of the stomach is stapled off would seem to be a reason. Patients literally can’t eat much. But the main effects—and what intrigues Dailey—likely stem from the additional “removal” of the upper small intestine. In bypassing the duodenum, where proteins, fats and sugars are broken down, the food that enters the lower gut (the jejunum) is now less well-digested. There aren’t so many amino acids, for example, as longer protein fragments. Also, more nutrients hit the jejunum than before the surgery.

What all that does, she’s found, is trigger the release of appetite-influencing hormones.

In a new study, Dailey and colleagues set rats up to model effects of the gastric bypass, gently infusing either small amounts of glucose, linoleic fatty acid or fragments of casein protein directly into the jejunum.

During the infusion and afterward, the team monitored how much the rats ate. Animals given glucose or the fatty acid had a significant drop in eating—a skipped meal, actually—maintained through the five days of testing. The rats lost weight. And most interesting was increased output of GLP1 and PYY, two intestinal hormones proven to decrease eating.   

“We believe this closely reflects what happens in humans after a Roux-en-Y,” she says. “It suggests that part of the benefits come because specific nutrients hit the lower intestine and trip hormones which make you less hungry.”

But Dailey believes the surgical effects are broader: Research suggests long-term changes occur in intestinal cells, ones that could prolong the more healthful eating habits. “Could you get an obese person’s intestine to behave like a lean person’s simply by altering what it’s exposed to?” she wonders. Her work to explore a long-term Roux-like infusion of nutrients is under way. 

Perhaps a coated capsule of the right fatty acid could slip unscathed through the upper GI tract to deliver its “payload” to the jejunum. Or perhaps, she says, a bioactive drug could directly mimic the hormones for the desired effect.

“These,” Dailey says, “are the cool possibilities that drive our work.”

For information: 410-955-2996.

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