‘Skinny gene’ offers obesity hope

Sometimes, science confirms what we feel we know.

It appears there is a genetic reason why skinny people stay slim.

In new preliminary research published in the journal Cell, scientists have isolated a gene that appears to help keep skinny people slim, potentially providing new treatments for obesity.

“We all know these people – it’s around one per cent of the population,” said senior author Josef Penninger, director of the Life Sciences Institute and professor of the department of medical genetics at the University of British Columbia.

He told sciencedaily.com: “They can eat whatever they want and be metabolically healthy. They eat a lot, they don’t do squats all the time, but they just don’t gain weight.”

Prof. Penninger’s team analysed DNA and clinical data from the Estonian Biobank, comprising 47,102 people aged 20 to 44, uncovering genetic variants in the ALK gene of thin individuals.

They concluded the gene may be involved in weight-gain resistance.

When they extended their study, the researchers found flies and mice without ALK remained thin and were resistant to diet-induced obesity.

“We gave the mice (what amounted to) a McDonald’s diet. The normal mice got obese and the ones without ALK remained skinny,” Prof. Penninger said.

“If you think about it, it’s realistic that we could shut down ALK and reduce ALK function to see if we did stay skinny,” he said.

“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.”

The New Daily science editor John Elder says the mouse studies suggested ALK also played a role in the brain “by instructing the fat tissues to burn more fat from food”.

The ALK gene makes a protein called anaplastic lymphoma kinase, which is involved in cell growth and has been investigated in cancer research.

Prof. Penninger’s study observed genetic maps of people with a BMI (body mass index) below 18 and compared them with those of people of normal weight.

University of Cambridge researchers had already concluded: “The genetic dice are loaded in favour of thin people and against those at the obese end of the spectrum.”

Stephen O’Rahilly, professor and head of the department of clinical biochemistry and the director of the Metabolic Diseases Unit at the University of Cambridge, said the new research “certainly increases interest in ALK7 inhibition as a therapeutic strategy for the treatment of obesity”.

Obesity is a major issue in western nations, where more than half of adult populations are at risk of disease because they are overweight. Diets loaded with added sugar and sedentary lifestyles are often cited as causes, but previous studies found “considerable individual variation in weight within a population that shares the same environment”.

Studies focused on overweight individuals indicated “variation in body weight is largely influenced by our genes”.

Prof. Penninger’s group turned the tables.

“Everybody studies obesity and the genetics of obesity,” he says. “We thought, ‘Let’s just turn it around and start a new research field.’ Let’s study thinness.”

Prof. Penninger says the findings are not “the ultimate answer”, but important “starting points”.

Are you one of those people who can eat what they want without piling on the kilos? Or do you know someone like that?

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Written by Will Brodie

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