Rare skinny gene predisposes some to being thin

Henrietta Strickland
May 23, 2020

Scientists have identified a gene they believe may be linked to thinness - and potentially to resisting weight gain.It is, they say, one of the few studies to look at how and why some people stay thin, rather than the causes of weight gain and obesity. All people in the study were considered to be "healthy, thin and normal weight", UBC said.

In a study published Thursday in the journal Cell, a group of global authors released their findings that individuals with certain variations in a gene known as ALK are physically more resistant to weight gain than most.

The Estonian Biobank was an was ideal start because of its size, wide age range and strong phenotype data, they say, but biobanks that collect biological or medical data and tissue samples don't have a universal standard in data collection, which makes comparability a challenge. ALK has a reputation as a gene which drives tumor developments, often mutating due to certain cancers, but relatively little is known about its noncancerous role.

They found that the test subjects who had been modified became resistant to diet-induced obesity, while mice and flies who had the same diet and level of activity, but retained the gene, weighed more and had more body fat.

O'Rahilly described the animal studies as "well done" but noted that the genetic variation that was associated with lower body mass index in the Estonia biobank was "modest" and not as robust as many experts in the field would accept as "definitive".

The team now plans to conduct more research, focusing on how ALK regulates brain chemistry and balances metabolisms to ward off obesity.

They found a mutation of the ALK gene among the thin group.

Why can some people eat as much as they want, and still stay thin?

"It's possible that we could reduce ALK function to see if we stay skinny", Penninger said. He says it's a realistic possibility because ALK inhibitors are already used in cancer treatments. "It's targetable. We could possibly inhibit ALK, and we actually will try to do this in the future". The team says its findings need to be confimed through a meta-analysis with other data banks. "You learn a lot from biobanks", says Penninger.

The team then examined how the ALK gene functions in mice and flies. "The normal mice got obese and the ones without ALK remained skinny", Penninger said. "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". W.H. was supported by a grant from the European Community's Seventh Framework Programme, the Research Institute of Molecular Pathology (IMP), Boehringer Ingelheim, the Austrian Research Promotion Agency, IMBA, the Austrian Ministry of Sciences, the Austrian Academy of Sciences, an ERC Advanced Grant, and an Era of Hope Innovator award.

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