The Colgate Scene
March 2007

Waging a war on obesity
Researcher Rudolph Leibel is leading the charge against an epidemic

[Photo by Timothy D. Sofranko]

When Dr. Rudolph Leibel '63 says it will one day be possible to control and prevent human obesity and its sister epidemic, diabetes, it means something.

Today the co-director of the internationally recognized Naomi Berrie Diabetes Center and professor of pediatrics and medicine at Columbia University, Leibel has spent the greater part of his professional career studying the control of body weight, the biology of fat tissue, and the relationship between body fat and susceptibility to diabetes.

He has published papers on adipose (fat) tissue, genes that cause obesity, the physiology of obesity, and a host of other related topics. He talks about mouse obesity and diabetes-related mutations the way most people chat about the weather.

So while reining in these diseases, as scientists eradicated smallpox in the 1900s, may sound like fantasy to some, there is no question in Leibel's mind that it can happen. Since the late 1970s, he and a group of colleagues have been leading the charge against obesity and diabetes. His contributions have given the scientific community a better understanding of the genetics of obesity, and paved the way for subsequent breakthroughs that have moved researchers several steps closer to changing the lives of what the Centers for Disease Control estimates to be the 60 million Americans with the illness.

"Many have said that obesity is the single-most important medical problem in developed and, increasingly, underdeveloped countries because of its link to diabetes, high blood pressure, stroke, and certain kinds of cancers," he said recently in his laboratory in the Naomi Berrie Diabetes Center at Columbia University Medical Center in Manhattan. "It's clear that this is a very important and costly problem."

For all of Leibel's straightforwardness about the graveness of the illness, he is equally matter-of-fact in his resolve to fight it. And the good news for patients is that he is still waging his war.

From foot solider to general
Leibel's career began like many professionals in health-related fields: in the examining room. After graduating from Colgate in the early 1960s with a degree in English, he earned an MD from the Albert Einstein College of Medicine in the Bronx, N.Y., and moved to Boston, where he interned at Massachusetts General Hospital. Following a two-year stint in the U.S. Army Medical Corps, he held positions at Children's Hospital, Massachusetts General, the Cambridge Hospital, and the Department of Nutrition and Food Science at the Massachusetts Institute of Technology, where he also taught and conducted research.

He always had an interest in obesity research, he said, but it wasn't until one day several years into his tenure as a pediatrician in Boston that Leibel had a wake-up call. A concerned mother had brought in her severely obese son for a checkup. At the end of the appointment, she asked how she could help her son reach a healthy body weight. Leibel was about to detail some of what he called the "conventional approaches" of dropping pounds, but then stopped himself.

"I said to her, `I could tell you a bunch of things people have tried, but I'm not really convinced that any of this is going to work. As a matter of fact, I'm pretty sure they won't,'" he recounted. "So she turned to the boy and said, `Randall, let's get out of here. This doctor doesn't know s—-!'" Leibel shook his head with an ironic laugh. "I was thinking to myself, you know, this woman's got a point." It was at that moment that he decided to make a change in his life, he said. "I didn't want to just stand around and complain about things. I had to do something."

After much soul-searching and discussion with his wife, Leibel packed up his young family and shipped out to New York, where he had been offered a position as a research scientist and faculty member at Rockefeller University. The pay was half the salary of his previous job, but it was where he wanted to be — in the trenches. It would also enable him to work with some of the world's top scientists in the field, leading to numerous collaborations with organizations around the world in the years that followed.

The battle and its ammunition
Throughout nearly three decades in the lab, Leibel has since examined the biological bases for the maintenance of body weight, specifically the complex relationship between metabolism, hormones, and obesity. But when he first began his studies at Rockefeller in 1978, his focus was on the biochemistry of human adipose tissue. Later, Leibel shifted his attention and energy to the role that genetics plays in obesity.

That decision paid off; in 1994, he and his colleagues discovered the hormone leptin, which signals the brain that the body has enough fat to survive and procreate and plays a critical role in regulating weight. This work also led to the identification of the receptor for leptin.

Knowing more about leptin was an important development for the field, and it changed the prevailing wisdom about the main cause of obesity, said Robin Goland, co-director of the Naomi Berrie Diabetes Center and the Florence Irving associate professor of medicine. Previously, scientists believed that obesity was a result of the voluntary behavior of patients, but Leibel's research showed that it has more to do with molecular physiology than willpower.

"The discovery of leptin was a huge breakthrough," said Goland, "and Rudy was a major leader and pioneer who inspired much of this work. He has had an enormous impact on the field of obesity research."

Since the leptin coup, Leibel's passion for his studies has continued. He and his team are now trying to identify genes related to obesity and/or Type 2 diabetes in mice and humans. They are also investigating the possibility that giving obese patients low doses of leptin may help them maintain a reduced body weight. And, Leibel said, riding the elevator up to his lab in the Naomi Berrie Diabetes Center with patients every day "keeps you honest." It is a constant reminder of what his ultimate objective is: to put himself out of work.

"I'd like for the day to come where we don't need to have a diabetes center or an obesity center or any of these places," Leibel explained, gesturing at his office. "It would be great if we could actually shut this place down, like the old tuberculosis sanatoriums from the past. I'm absolutely sure it will happen — I just hope it's in my lifetime."

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