Medical Device Daily Senior Staff Writer

CLEVELAND – A gathering focused on obesity, as the Cleveland Clinic's 2010 Medical Innovation Summit was last week, simply would not be complete without at least one speaker examining the genetics behind the disease. And few would be more qualified to lead such a discussion than Jeffrey Friedman, MD, PhD.

Friedman, a physician scientist studying the genetic mechanisms that regulate body weight, was recently honored for discoveries that led to the identification of leptin, a hormone that regulates appetite and body weight. According to the Cleveland Clinic, Friedman's finding has helped demonstrate that obesity can be a result of metabolic and hormonal disruptions rather than lack of willpower.

Friedman, a professor at the Rockefeller University (New York), an investigator at the Howard Hughes Medical Institute (Chevy Chase, Maryland) and the director of the Starr Center for Human Genetics (New York), kicked off his discussion by showing two photographs, side by side, of two seemingly very different children. The child on the left clearly suffered from morbid obesity. The child on the right appeared lean and healthy.

"How is it that the body weight of these two individuals can differ so dramatically," Friedman asked, pointing out that many people would respond that "lack of willpower" was the culprit, and that lifestyle and environmental factors must be to blame.

"People argue that our genes haven't changed, so it must be the environment," Friedman said.

Towards the end of his discussion, Friedman revealed that the two photographs were actually of the same child. The young boy had a mutation in the gene that produces the hormone leptin, causing him to have an increased appetite.

According to Friedman, leptin is made of fat tissue and sends a signal informing the brain that there are adequate stores of energy. When leptin drops, appetite increases.

The boy in the photograph Friedman shared had a normal birth weight but was morbidly obese starting in infancy, was over-eating, and had very high insulin levels. At age 4, the child ate 1,125 calories at a single meal and weighed 90 pounds.

After being injected with leptin, the boy's calorie intake dropped to about 180 calories per meal and he weighed 72 pounds.

Friedman wrote an editorial last year that was published in Newsweek, "The real cause of obesity," in which he also mentioned the leptin-deprived child and said that the hormone levels were the only thing that changed from the time he was a morbidly obese four year old and a normal weight six year old. "His parents weren't more or less permissive, his snacks did not switch from processed to organic, his willpower was not bolstered. Rather the boy was a victim of a malfunctioning weight-regulating system that led to an uncontrollable drive to eat."

Friedman's research on various aspects of obesity received national attention in late 1994, when it was announced that he and his colleagues had isolated the mouse ob gene and its human homologue. They subsequently found that injections of the encoded protein, leptin, decreases body weight of mice by reducing food intake and increasing energy expenditure. Current research is aimed at understanding the genetic basis of obesity in humans and the mechanisms by which leptin transmits its weight-reducing signal.

Friedman noted that mutations in the leptin gene are rare, but that 10% of morbidly obese people carry defects in genes that regulate food intake, metabolism, and body weight. "The evidence further indicates that the rest of the obese population carries genetic alterations in other, as yet unidentified, single genes or combinations of genes (polygenes) interacting with environmental factors," he wrote.

But the idea that obesity may be genetic, rather than a lifestyle choice, is not yet a widely-accepted view among the general population.

During his presentation last week Friedman lightened the mood by sharing some of the feedback he received in reaction to his editorial in Newsweek. The bulk of these comments were things like, "this is crap," "what a complete load of crap," or – Friedman's favorite – "are we animals or do we have an intellect and the ability to chose how we behave?"

Throughout the summit held last week in Cleveland many of the panelists and attendees were asserting that America needs to declare a war on obesity. Take the first day of the conference, for example, when a panel of executives from the "top of the industry" examined the obesity threat and Stryker (Kalamazoo, Michigan) CEO Stephen MacMillan said that "to keep our citizens and country financially and physically fit we have to declare nothing less than a war on obesity," (Medical Device Daily, Nov. 3, 2010).

Friedman did not argue with that point but he did ask that the medical community declare a "war on obesity - not the obese," making the point that the focus should be more on health than appearance.

Amanda Pedersen, 309-351-7774;

amanda.pedersen@ahcmedia.com

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