The study subjects had been thin all their lives, and not because they had unusual metabolisms. They just did not care much about food. They never ate enormous amounts, never obsessed on the next meal. Now, a group of researchers in Britain may have found the reason.
The people carry a genetic alteration that mutes appetite. It also greatly reduces their chances of getting diabetes or heart disease.
The scientists’ study, published in ‘Cell’, relied on data from the UK Biobank, which includes a half million people aged 40 to 69.
A second study in the same journal also used data from this population to develop a genetic risk score for obesity. It can help predict, as early as childhood, who is at high risk for a lifetime of obesity and who is not.
Together, the studies confirm a truth that there are biological reasons that some struggle with their weight and others do not. The biological impacts often are seen on appetite, not metabolism. People who gain too much weight or fight to stay thin feel hungrier than naturally thin people.
The study of the appetitedulling mutation was led by Sadaf Farooqi, professor of metabolism and medicine at the University of Cambridge, and Nick Wareham, an epidemiologist at the university.
The study drew on Farooqi’s research into a gene — MC4R. People with MC4R mutations tend to be obese. Experts have recorded as many as 300 mutations in this gene, and they are the most common single-gene cause of obesity.
The mutations destroy satiety, the feeling of fullness after a meal, Farooqi found.
Normally, when people eat a meal, the gene is switched on and sends a signal telling people they are full. Then the gene turns itself off. But some people carry a rare mutation in MC4R that prevents the gene from working. Their bodies never get the signal that they have eaten enough.
In the new study, Farooqi found that in some thin people, the MC4R gene is always turned on, instead of always off, because of different mutations involving a previously unknown metabolic pathway. They continually feel satiated.
Researchers are finding that appetite and satiety determine who gains excess weight and who does not, noted Cecilia Lindgren, professor at the University of Oxford. “We think regulation of hunger and satiety is the key,” she said.
In the other study of UK Biobank data, Dr Amit V Khera, a cardiologist at Massachusetts General Hospital, and his colleagues sought a way of predicting who is destined to be fat or to struggle with weight, and who would be spared a weight problem.
The scientists put together an obesity risk score based on DNA alterations at 2 million places in the genome. People with the highest scores weighed 30 pounds more on average than those with the lowest scores. Among the very obese, 60% had a high score.
But the UK Biobank population consisted only of adults. “We wondered, when does this start?” said Sekar Kathiresan, co-author of the paper.
At birth, babies with high scores weighed the same as babies with low scores, the scientists found. By age 3 1/2, they were clearly heavier on average than others their age. By age 8, the children often were obese, and by late adolescence they weighed on average 30 pounds more than those with low risk scores.
The people carry a genetic alteration that mutes appetite. It also greatly reduces their chances of getting diabetes or heart disease.
The scientists’ study, published in ‘Cell’, relied on data from the UK Biobank, which includes a half million people aged 40 to 69.
A second study in the same journal also used data from this population to develop a genetic risk score for obesity. It can help predict, as early as childhood, who is at high risk for a lifetime of obesity and who is not.
Together, the studies confirm a truth that there are biological reasons that some struggle with their weight and others do not. The biological impacts often are seen on appetite, not metabolism. People who gain too much weight or fight to stay thin feel hungrier than naturally thin people.
The study of the appetitedulling mutation was led by Sadaf Farooqi, professor of metabolism and medicine at the University of Cambridge, and Nick Wareham, an epidemiologist at the university.
The study drew on Farooqi’s research into a gene — MC4R. People with MC4R mutations tend to be obese. Experts have recorded as many as 300 mutations in this gene, and they are the most common single-gene cause of obesity.
The mutations destroy satiety, the feeling of fullness after a meal, Farooqi found.
Normally, when people eat a meal, the gene is switched on and sends a signal telling people they are full. Then the gene turns itself off. But some people carry a rare mutation in MC4R that prevents the gene from working. Their bodies never get the signal that they have eaten enough.
In the new study, Farooqi found that in some thin people, the MC4R gene is always turned on, instead of always off, because of different mutations involving a previously unknown metabolic pathway. They continually feel satiated.
Researchers are finding that appetite and satiety determine who gains excess weight and who does not, noted Cecilia Lindgren, professor at the University of Oxford. “We think regulation of hunger and satiety is the key,” she said.
In the other study of UK Biobank data, Dr Amit V Khera, a cardiologist at Massachusetts General Hospital, and his colleagues sought a way of predicting who is destined to be fat or to struggle with weight, and who would be spared a weight problem.
The scientists put together an obesity risk score based on DNA alterations at 2 million places in the genome. People with the highest scores weighed 30 pounds more on average than those with the lowest scores. Among the very obese, 60% had a high score.
But the UK Biobank population consisted only of adults. “We wondered, when does this start?” said Sekar Kathiresan, co-author of the paper.
At birth, babies with high scores weighed the same as babies with low scores, the scientists found. By age 3 1/2, they were clearly heavier on average than others their age. By age 8, the children often were obese, and by late adolescence they weighed on average 30 pounds more than those with low risk scores.