Genes May Spur Some Childhood Obesity

Mutations change activity of 'fat hormone' leptin, researchers say

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HealthDay Reporter

WEDNESDAY, Jan. 17, 2007 (HealthDay News) -- Mutations in a gene governing the "fat hormone" leptin could explain some cases of childhood obesity, researchers report.

Leptin is a hormone that helps regulate energy intake, and mutations in the leptin gene have been linked to early-onset obesity.

"We have been trying to find genes which when disrupted cause obesity in some patients," said study author Dr. I. Sadaf Farooqi, from Addenbrooke's Hospital, in Cambridge, U.K. "To date, there are seven known gene defects that cause obesity," she said.

Her team's report appears in the Jan. 17 issue of the New England Journal of Medicine.

This same research team had previously shown that people with a defect in leptin tend to become severely obese.

People underestimate the importance of genes in controlling weight, Farooqi said. "We think there are a lot more genes to find. Obesity is a complex problem, and genes play an important role in determining weight," she noted.

In this study, Farooqi's team sequenced the leptin-receptor gene in 300 adults and children who had severe early-onset obesity, including 90 family members. Among these people, the researchers looked for common mutations in the gene.

Out of the 300 people, 8 (3 percent) had mutations in their leptin-receptor gene. Each the nine mutations detected influenced the ability of the receptor to signal correctly. People with these mutations were severely obese and also had changes in their immune system function and delayed puberty.

Although these mutations were found in a group of people who were obese starting from childhood, Farooqi believes the mutations may have links with adult obesity, too.

Before this study, only one family had been identified with these mutations in the leptin-receptor gene. "Now we have found another 10 families," Farooqi said.

The findings could lead to new treatments for obesity, she added.

"This is another piece in the puzzle of finding pathways that are involved in controlling weight. It teaches us more about how leptin signals in the brain and provides a template for finding better ways to prevent and treat obesity," Farooqi said.

Another expert agreed.

"This is a positive advance in our knowledge of obesity," said Yvon Chagnon, director of the Genomic Laboratory at Laval University Research Center, Quebec, Canada. "But it will not explain a lot of cases of obesity in the general public," he added.

Chagnon noted that probably 50 percent of obesity is the result of genes. "For these people, we have to find some markers to identify these people and give them the right diagnosis and the right treatment," he said.

Diet and exercise isn't enough for these patients, Chagnon said. "Knowing the origin of their problem will help in choosing the best treatment and in developing new treatments," he said.

More information

Find out more about childhood obesity at the U. S. National Heart, Lung, and Blood Institute .

SOURCES: I. Sadaf Farooqi, M.B., B.S., Ph.D., Addenbrooke's Hospital, Cambridge, U.K.; Yvon C. Chagnon, Ph.D., director, Genomic Laboratory, Laval University Research Center, Quebec, Canada; Jan. 18, 2007, New England Journal of Medicine

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