Scientists Discover So-Called ‘Skinny Gene’


New research offers answer as to why some can seemingly pig out on anything without gaining weight.


VIENNA — We all know that one person who can eat whatever they like and never gain a pound. Ice cream at 2 in the morning? Bring it on. A third, or fourth, slice of pizza? Sure, why not. For the rest of us, the genetic perks that these individuals enjoy can be frustrating to say the least. Now, a groundbreaking new international study appears to have zeroed in on the so-called “skinny gene” that help keep such individuals thin.

Scientists from Austria, Canada, and Estonia say that lower, or deficient, levels of the gene Anaplastic Lymphoma Kinase (ALK) are significantly linked to skinniness and bodily resistance to weight gain.

Scientists discover 'skinny gene'
Why some people eat as much as they want and stay lean while others can’t. In mice, genetic deletion of ALK resulted in thin animals with marked resistance to diet induced obesity while food intake was not changed. The researchers found that ALK in the hypothalamus controls energy expenditure via sympathetic control of adipose tissue lipolysis. The drawing illustrates how our genetic make-up determines body weight (gain). (Image ©IMBA/IMP graphics)

Most research projects focusing on weight loss and gain search for genes that cause obesity. This study is novel due to the fact that it focuses specifically for a gene linked to thinness instead.

When It Comes To ALK, Less Is More

Using an Estonian population sample of more than 47,000 people, the study’s authors performed a series of genome-wide association studies. By comparing especially thin people’s genes to individuals of an average weight, they were able to pick out ALK. Up until now, ALK has really only been known for the role it plays in some cancers, as it tends to mutate in numerous forms of cancer. That being said, its physiological purpose has always remained a mystery.

To test their theory that diminished levels of ALK are responsible for genetic skinniness, the research team performed an experiment in which they “deactivated” the ALK genes in a group of mice. To the researchers’ surprise, those mice immediately became skinnier despite continuing with the same diets and activity levels.

Similar results were also found when ALK genes were inhibited in a group of fruit flies.

“By using a technique called indirect calorimetry, we could show that ALK-deficient mice exhibit increased energy expenditure. This means that they burn more calories than normal mice and explains why they remain thin even if they eat the same amount of food. In addition to that, these animals also show improved glucose tolerance,” explains first author Michael Orthofer in a release.

ALK is most prominent in the body within a very specific brain region known as the paraventricular nucleus (PVN) of the hypothalamus. Incredibly, when ALK was diminished in this brain region alone, studied animals experienced very similar weight loss to full body ALK reductions.

“This strengthens the notion that ALK is indeed part of a larger brain circuit involved in energy expenditure. We are very excited about these results on the genetics of thinness and will further investigate the mechanisms of how ALK-expressing neurons are able to control weight. Our results also highlight the important therapeutic potential of ALK inhibition,” concludes Josef Penninger, IMBA group leader and founding director & director of the Life Sciences Institute of the University of British Columbia.

The study is published in Cell.

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