WHILE some have to hit the gym hard and stick to rigorous diets to stay in shape – others can stay slim effortlessly no matter what they eat.
But now scientists may have identified their secret – a "skinny gene" which may play a role in resisting weight gain.
And scientists say this gene could potentially be manipulated – and pave the way for new obesity treatments.
Researchers made the discovery while analysing a genetic database of more than 47,000 Estonians aged 20 to 44 to identify the gene believed to be key in keeping metabolically healthy people thin.
And they found that those who were healthy and thin tended to have certain variants of the ALK gene.
"We all know these people: it's around one per cent of the population," said Josef Penninger, professor of the department of medical genetics at the University of British Columbia, who led the study.
They don't do squats all the time but they just don't gain weight
"They can eat whatever they want. They don't do squats all the time but they just don't gain weight.
"Everybody studies obesity and the genetics of obesity – we thought, 'Let's just turn it around and start a new research field.' Let's study thinness."
In particular, through experiments on mice and fruit flies, Prof Penninger discovered that the ALK gene played a role in nerve cells in the hypothalamus region of the brain, which helps to regulate appetite.
This, in turn, appeared to influence part of the sympathetic nervous system and resulted in changes in how fat stores were used elsewhere in the body.
Helps regulate appetite
Deleting the gene created mice that stayed thin, even when fed an ultra high-calorie diet. Similarly, it made fruit flies lighter.
There is currently a high demand for new therapies to tackle obesity – particularly following the revelation that obesity doubles the risk of needing hospital treatment for coronavirus.
And more than six in ten adults in the UK are overweight and one in four is obese.
Professor Penninger believes ALK could one day be targeted with drugs to give people a better chance of staying a healthy weight.
How to tell if you're obese
The most widely used method to check if you're a healthy weight is body mass index (BMI).
BMI is a measure of whether you're a healthy weight for your height. You can use the NHS BMI healthy weight calculator to work out your score.
For most adults, a BMI of:
- 18.5 to 24.9 means you're a healthy weight
- 25 to 29.9 means you're overweight
- 30 to 39.9 means you're obese
- 40 or above means you're severely obese
BMI is not used to diagnose obesity because people who are very muscular can have a high BMI without much fat.
But for most people, BMI is a useful indication of whether they're a healthy weight.
A better measure of excess fat is waist size, which can be used as an additional measure in people who are overweight (with a BMI of 25 to 29.9) or moderately obese (with a BMI of 30 to 34.9).
Generally, men with a waist size of 94cm or more and women with a waist size of 80cm or more are more likely to develop obesity-related health problems.
The gene has also been shown to play a part in cancer and compounds have been developed to dampen down its activity.
"It's realistic that we could shut down ALK and reduce ALK function to see if we did stay skinny," he wrote in his paper, which was published in the journal Cell.
"ALK inhibitors are used in cancer treatments already. It's targetable. We could possibly inhibit ALK, and we actually will try to do this in the future."
Despite this, other researchers cautioned that tinkering with ALK could have unwelcome side-effects and said that convincing genetic studies of weight have suggested that large numbers of genes combine to determine a person's weight.
The next step is to carry out what scientists call a 'meta-analysis' which will involve pooling data from other other data banks, including the UK Biobank that holds genetic information on half a million Brits, to see if they get the same results.
Prof Penninger said: "You learn a lot from biobanks. But, like everything, it is not the ultimate answer to life.
"But they are the starting points and very good points for confirmation, very important links and associations to human health."
The team says that its work is unique. It combines exploration of the genetic basis of thinness on a population with genome-wide scale and analyses of living organisms – mice and flies.
Prof Penninger added: "It is great to bring together different groups, from nutrition to biobanking, to hardcore mouse and fly genetics.
"Together, this is one story including evolutionary trees in metabolism, the evolutionary role of ALK, human evidence, and hardcore biochemistry and genetics to provide causal evidence."
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