MEDFORD, Mass. (AP) – What if, instead of having to exercise to burn off fat, your fat cells would do it for you?

A Tufts University chemical engineer, Kyongbum Lee, is working on a novel way to treat obesity that he says may do just that.

Lee, 35, says five years of research have shown initial proof of concept that it is possible to manipulate metabolic reactions in fat cells to make them dump excess nutrients that might otherwise be stored as fat.

Lee has had no formal medical or biology training and relied on medical researchers for some advice and guidance. His methods, however, were unusual as he applied an approach typically used by chemical engineers to methodically analyze key reactions in fat cells to figure out which ones could be tinkered with to produce the biggest impact without affecting anything else.

The basic research at Tuft University’s School of Engineering – partly funded by $750,000 in grants from the National Institutes of Health and the National Science Foundation – illustrates desperation in the search for new ways to treat obesity as non-medical experts venture into a field dominated by traditional medical scientists.

Humans have trouble shedding excess weight because of their evolution from hunter-gatherers whose bodies developed an efficient system to store nutrients and energy as fat because ancient conditions did not guarantee that they could find a meal everyday.

“We were not necessarily built for the refrigeration age,” Lee said. “So, it made a lot of sense for people to store energy in the form of fat … If you go hungry for several days, you start burning off extra calories.”

His research, however, seeks to change that by essentially curbing the efficiency of the fat cell, forcing it to burn off larger volumes of the stored fat to produce sufficient calories needed by the body.

“The fat cell is a very efficient user of energy. It is, by evolution, one of the few cell types that really can squeeze a lot of energy out of its nutrient fuel – so what we are trying to do is go against the grain a little bit and make it less efficient in using the energy, not by a lot, but just a little bit,” Lee said. “This is one of the few cases where being wasteful is actually a good thing.”

Lee is now working to refine and advance his research, and says it may take several years before it could be translated into noninvasive drugs for obesity. In the meantime, peers are reviewing his initial work before it is accepted for publication.

He said the idea is not to engineer rapid, massive weight loss that is harmful to the body.

“The idea is, actually, to try to nudge your cell metabolism in the right direction over a period of time so there is a better balance of storage and accumulation of your nutrient fuel,” said Lee, an assistant professor at the chemical and biological engineering department.

Lee is among many chemical and biological engineers in laboratories across the nation studying the smallest unit of life that stores, breaks down and manages the body’s fat – a fat cell – in an effort to craft ways to combat obesity, said professor Shankar Subramaniam of the chemistry and biochemistry department at the University of California at San Diego.

“The overall idea is good, but the devil is in the details,” said Subramaniam, whose lab is also working on engineering obesity and whose work is not affiliated with Lee’s research.

Lee’s search for a cure to obesity was triggered by a 2002 mistake he made in the lab during a Massachusetts Institute of Technology’s graduate course he took at Massachusetts General Hospital. He was making a solution used to culture a cell and says he must have done something wrong – the liver cells he was examining started to accumulate fatty compounds, which is not normal in a healthy liver, he said.

That mistake sparked the idea that he might be able to use chemicals to manipulate fat cells to treat obesity.

A year later, he joined the faculty at Tufts and opened his own lab to study the issue. “Sometimes interest occurs because you screw up,” he said, laughing. “In this case, I did.”

AP-ES-03-08-08 1520EST


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