A trio of relatives from Turkey who share an extremely rare genetic mutation that results in severe obesity have lost nearly half their body weight after being treated with shots of the hormone leptin.
The three Turkish family members -- the only known adults in the world who carry the genetic mutation -- are unable to produce enough of this key hormone, which is linked to appetite control.
In this study, Dr. Julio Licinio, a professor of medicine at the David Geffen School of Medicine at the University of California at Los Angeles, flew in the three cousins -- two women and one man -- from their small village in Turkey last September. Licinio had met the family when he spent a month traveling in Turkey in 1998 and after reading medical literature about obesity. The cousins ranged in age from 27 to 40 and all were morbidly obese. The youngest cousin still showed signs of prepubescence.
"We hypothesized that leptin deficiency may lead to obesity and, in some cases, delay sexual and psychological maturity," Licinio said. He further explained that leptin long had been considered a key to weight control. More recently, however, researchers discovered obese people produce too much of the hormone and their bodies simply stop responding to its appetite cues.
When the trio arrived in Los Angeles, they immediately began taking daily leptin injections. After ten months, each patient had lost half his or her body weight -- more than 150 pounds.
The leptin therapy produced other outcomes as well. The 27-year-old patient showed physiological changes signaling sexual maturity. Licinio said the hormone deficiencies may have stunted his sexual development. The cousins' dispositions also changed quickly. After only two weeks of the injections, the researchers noticed the patients grew noticeably more assertive and independent.
"The subjects' personality changes suggest that there is a relationship between fat and how we feel," Licinio said, adding UCLA plans to explore leptin's link to mood disorders.
Another striking finding: when the trio's brains were measured using magnetic resonance imaging, or MRI, the scans revealed "that the organs had expanded a small but significant amount," Licinio said. "While the relevance of this outcome is currently unclear, it poses the first known instance of brain growth in adults," he said.
Earlier research on animals born without the ability to manufacture leptin showed they possessed brains 30 percent smaller than normal. Until now, however, researchers never had studied the effect on human brain size and growth of leptin deficiency and replacement.
Still, the most pronounced result of the therapy was the weight loss.
"I had no idea it would this dramatic," Licinio told United Press International. "I was very, very surprised. My initial thought was they would lose some weight and then it would plateau."
The huge drop in weight also was a wonderful surprise for Bayram Donsak, the 27-year-old patient. Speaking through an interpreter, Donsak told UPI the leptin treatment changed his life.
"I feel wonderful," he said. "I feel very light and everything is beautiful to me right now." Prior to the leptin treatment, Donsak said he "was unhappy and very, very heavy and I couldn't carry my own body." He went from 142 kilos (313 lbs.) to 75 kilos (165 lbs.). He said he felt shy around people because they made fun of him and he did not go out much. Now he is looking forward to returning to his village in Ankara this Saturday after 13 months in the United States.
"Everybody is going to be very happy and I know they're going to be really surprised when they see me," Donsak said. Asked if he would diet, he replied he would continue eating the foods he enjoys, but now plans to incorporate exercise, especially walking, into his life. He also will continue to take leptin injections. "I'm very happy someone found out about this medicine," he said.
Leptin is made in fat cells and signals to the brain when to stop eating. It also helps regulate sexual development and even helps the immune system fight illness, especially in childhood. Licinio said leptin replacement therapy could benefit obese individuals who lack sufficient leptin levels. The only side effect, Licinio said, was a minor rash at the injection site on one of the patients. UCLA is expanding its research on the role of leptin and obesity, he said.
Dr. Ronald Weinsier, professor and director of the Clinical Nutrition Research Center at the University of Alabama at Birmingham, said although the findings are striking, they probably do not apply to the masses of people who are clinically obese.
"It is important that we (the public and researchers) understand that only in very rare cases is a person born without the ability to produce the hormone leptin," Weinsier told UPI. "In fact, essentially all overweight and obese persons have increased, not decreased, level of leptin ... Thus, while the findings in these unusual cases are important from the standpoint of researchers' understanding the role of leptin in appetite and weight control, they are likely to have little or no relevance to the vast majority of persons worldwide who are challenged with maintaining a normal body weight."
In the United States, 61 percent of adults are considered overweight or obese, according to the Surgeon General's office. Obesity is defined as having a body mass index of 30 or higher. Body mass index is a calculation based on height and weight.