Weight Gain’s Connection to One Gene

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Perhaps weight gain is not simply a matter of self-control.

Researchers at Boston Children’s Hospital published a study this week in the journal, Science, that says one gene is specifically related to weight gain. The paper’s lead author, Dr. Joseph Majzoub, chief of endocrinology at Boston Children’s Hospital and pediatrics professor at Harvard University, says that it may suggest that other genetic pathways are also related to weight gain.

Researchers isolated a gene called MRAP2 in mice that works with another gene known for regulating appetite. Researchers removed the MRAP2 gene from some mice, and in others, the gene was left alone. The mice were monitored from birth to death, and put on a very strict diet of an amount of food typical for a lean mouse. Despite the food restriction, mice without the MRAP2 gene quickly became overweight—weighing more than twice as much as a lean mouse.

For the mice without the gene to develop normally, researchers needed to reduce their food intake by 10 to 15 percent compared to the unaltered mice’s meals. “How many obese people do we know that tell us, ‘You know, I don’t eat any more than my friends and I don’t know why I’m overweight’ and we look at them and think, ‘They must not be adding up all the calories they’re eating,’” Majzoub says. “This puts obesity in a different light I think because many of us think of it as a lack of self-control but if it’s your metabolism that is more efficient at turning food into fat, then it’s certainly not a lack of self-control.”

The gene is also found in humans. Majzoub collaborated with Dr. Sadaf Farooqi of the University of Cambridge, who has been studying the genetics of a group of 500 obese people, and surveyed their genes in search of MRAP2 mutations. Of the 500, one had a gene-disabling mutation and three others had mutations that are believed to render the gene nonfunctional. This is less than one percent of the group, but this is also only examining the MRAP2 gene. “My vision is that it’s not going to be just one gene that causes obesity if it’s genetic,” Majzoub says. “It’s going to be a combination of genes.”

Majzoub says that this study is the start of discovering more elaborate genetic pathways related to obesity, and that perhaps a number of small mutations in a number of genes could also disrupt metabolic pathways and be a cause for obesity.

Continued studies will show how common genetics may be a cause of obesity. And someday, it could go even further. “We are beginning to look for drugs that might act as super-active versions of MRAP2 and that might be even more effective in suppressing weight gain,” Majzoub says, “but we’re just beginning.”