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This genetic mutation makes people feel full – all the time



The subjects had been thin all their lives, not because they had unusual metabolic processes. The food just did not matter to them.

They never ate huge amounts and were never obsessed with the next meal. Now, a group of researchers in the UK might have found the reason.

Humans carry a genetic change that dampens their appetite. It also reduces their chances of getting diabetes or heart disease.

The study published in the journal Cell on Thursday was based on data from the British biobank, which includes half a million people between the ages of 40 and 69, provided DNA samples and medical records, and allowed researchers to obtain their own To track health status for years.

The mutations destroy the satiety, the feeling of fullness after a meal. Farooqi and her colleagues found.

Usually, the gene is turned on when people eat a meal, and a signal is sent that people are full. Then the gene turns off. However, some people have a rare mutation in MC4R that prevents the gene from functioning.

As a result, their bodies never receive the signal that they have eaten enough. They always feel hungry and are often overweight. Your risk for diabetes and heart disease is 50 percent higher compared to those without a mutation.

In the new study, Dr. Farooqi and her colleagues found that in some thin individuals, the MC4R gene is always on instead of always off, as several mutations involved a previously unknown metabolic pathway .

These people are constantly fed up. About 6 percent of the population carry such protective mutations.

"This proves that MC4R is an important, if not the most important, weight controller," Dr. Farooqi. And the new route represents an obvious target for anti-obesity drugs.

Researchers are increasingly finding that appetite and satiety determine who gets overweight and who does not [C] Cecilia Lindgren, Professor of Genomic Endocrinology and Metabolism at the University of Oxford.

"We think that regulation of hunger and satiety is the key," she said. "There is food everywhere. If you are a bit hungry and someone puts on a big plate of donuts at your meeting, who will pick up the donuts?

In the other study of British biobank data, Dr. Ing. Amit V. Khera, a cardiologist at the Massachusetts General Hospital, sought out a way for his colleagues to predict from a vast collection of tiny variations in DNA who is destined to be fat or to fight weight, and who to Weight problem would have.

The scientists assembled an adiposity risk score based on DNA changes at two million sites in the genome. People with the highest ratings weighed an average of 30 pounds more than those with the lowest ratings. Among the very obese, 60 percent had a high score.

"We were shocked by the difference," Dr. Sekar Kathiresan, co-author of the newspaper and geneticist at the Massachusetts General Hospital.

However, the UK Biobank population consisted only of adults. "We were wondering, when does that start?" Kathiresan.

The researchers turned to additional data and confirmed their findings to 300,000 participants in other genetic studies. Babies with high ratings weighed just as much as babies with low ratings at birth.

At the age of 3 1/2 years, however, they were on average significantly heavier than others of their age. At age 8, children were often obese, and in late adolescence they weighed on average 30 pounds more than low-risk children.

A high score "is not deterministic," Dr. Kathiresan. "That does not mean that you're doomed to failure just because you're in the top percentile." A high score, however, means that weight control can be a struggle.

Dr. Joel Hirschhorn, a geneticist at Boston Children's Hospital, found that most of the sites in the genome that make up the risk score have nothing to do with weight. It is not yet clear which ones are most important.

He was impressed by the fact that obesity does not seem to be really solid until the kids are 8 years old. "These eight years could be magical and give you a unique opportunity to make a difference," he said.

That may not be easy, noted Ruth Loos, director of the Obesity Genetics Program at the Icahn School of Medicine at Mount Sinai. Children who are always hungry find ways to eat more.

"In an environment like ours, there is a lot of seduction," she said.

Cheap, tasty and high-calorie foods are available almost everywhere and snacks and pastures are commonplace. Those at high risk for obesity may be more easily seduced, "Dr. Loos.

Risk ratings, however, may indicate strategies that could work, Dr. Lee M. Kaplan, Director of Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital.

Among the 10 percent of the population with the highest risk ratios, many are not fat. Why this?

Are there hitherto undiscovered genes that counteract those that force people to overeat? Or do these people have good strategies to deal with hunger and control food?

"The bottom line is a whole series of new questions that can be asked and answered. Kaplan.


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