Could severe obesity be in the genes?


Could severe obesity be in the genes?

Scientists have discovered a particular gene mutation that could be linked to a cause of severe obesity.

Researchers from Boston Children's Hospital carried out a number of genetic surveys in several groups of people suffering from obesity, as well as a series of genetic experiments in mice.

The research, published in the journal Science, analyzed a gene called Mrap2 in different groups of mice. This particular gene has a human counterpart, which according to the scientists appears to be involved in regulating metabolism and food consumption.

Mutation of the Mrap2 gene

The researchers explained that the protein encoded by the Mrap2 gene sends a signal to a receptor in the brain called Mc4r. This receptor assists in increasing the metabolism and decreasing appetite in a "signaling chain" involved in energy regulation.

They explain that fat cells produce a hormone called leptin. This hormone triggers receptors in the brain to start the production of a second hormone called aMSH.

Mrap2 helps Mc4r detect the aMSH hormone, which essentially leads to a drop in appetite and weight. The scientists explain that any mutations in this signaling chain are likely to increase the risk of obesity.

What did the results show?

A study on mice revealed a mutation in the Mrap2 gene which could lead to obesity. Photo credit: Boston Children's Hospital.

The researchers analyzed two groups of mice. One group who had the Mrap2 gene removed from just the brain, and one group who had the gene removed from "whole-of-body."

Both groups of mice grew to around twice their normal size, but weight gain was greatest in those with the gene removed completely.

However, the mice who had had one working copy of the gene removed still showed an increase in appetite and weight gain.

The study authors say it was surprising that the mice without the Mrap2 gene did not eat more at first, but still continued to gain weight at a faster pace than the mice who did have the gene.

Joseph Majzoub, endocrinology chief at Boston Children's Hospital, says of the experiment:

These mice aren't burning the fat, they're somehow holding onto it. Mice with the genetic mutation gained more weight, and we found similar mutations in a cohort of obese humans."

Link to human obesity?

As part of the study, the researchers investigated various groups of people suffering from obesity from all over the world.

Of 500 people analyzed, there were four mutations in the human equivalent of the Mrap2 gene in patients suffering from severe, early-onset obesity. All of the patients affected had one copy of the mutation.

Although these findings suggest that the mutation of this gene could directly cause obesity in less than 1% of the obese population, the scientists believe there is a possibility that other mutations in the gene could be more common. They add that the mutated gene could also interact with environmental factors and other mutations that could lead to obesity.

Joseph Majzoub says: "We found other mutations that weren't as clearly damaging to the gene. It's possible that some of these more common mutations actually are pathogenic, especially in combination with other genes in the same pathway."

From this research, the scientists say further investigation is needed in larger groups of the obese population. They say they would like to analyze their activity and diet, and explore how the Mrap2 gene alters energy balance.

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