We all know the skinny type. They can eat whatever they want, spend zero time in the gym, and don’t put on an ounce. Now, according to new preliminary research published Thursday in the journal Cell, researchers may have found a gene that makes these super-skinny individuals remain so slim, possibly opening up a new frontier in obesity treatment.
An international team of scientists claimed they found a genetic variant unique to skinny individuals in what is known as the ALK gene. The ALK gene makes a protein called anaplastic lymphoma kinase which is related to cell growth. The variant was detected by looking at DNA samples and clinical data from more than 47,000 healthy people in Estonia between the ages of 20 and 44.
“The Estonia biobank is very unique in its detail,” said senior author Josef Penninger, a professor in the department of medical genetics and the director of the Life Sciences Institute at the University of British Columbia.
“We looked at the genetic maps of people with a BMI [body mass index] below 18 and compared them with those of people of normal weight and found the [genetic variant] that correlated with being super skinny,” Penninger said.
The team then looked at how the ALK gene works in mice and flies. Stephen O’Rahilly, Professor and Head of the Department of Clinical Biochemistry and Director of the Metabolic Disease Unit at the University of Cambridge, said the study was “not definitive” but “very interesting.”
O’Rahilly, who wasn’t involved in the study, added that “it certainly increases interest in ALK7 inhibition as a therapeutic strategy for the treatment of obesity.”
Thinner flies and mice
Scientists already recognize that the mutated form of the ALK gene and protein can contribute to the development of cancer tumors, the study said. Gene and protein mutations have been identified in non-small cell lung cancer, anaplastic large cell lymphoma, and neuroblastoma, brain cancer.
A new result suggests that a particular mutation of the gene can play a significant role in thinness and resistance to weight gain. To confirm this, scientists performed experiments on flies and mice and found that the elimination of this gene resulted in smaller versions of these flies and mice.
“We gave the mice (what amounted to) a McDonald’s diet. The normal mice got obese and the ones without ALK remained skinny,” Penninger said.
The team’s mouse experiments also indicated that the ALK gene would instruct fat tissues to consume more fat from food. O’Rahilly identified the animal studies as “well performed” but acknowledged that the genetic variation associated with the lower body mass index in the Estonian biobank was “modest” and not as strong as other field experts might consider as “definitive.”
However, he said that prior studies in much larger populations showed a suggestive, but not solid, a sign of association with body weight in that genome area, and it was unlikely that the variation would be specific to Estonians. Penninger said that gene-targeting treatments could help scientists fight obesity in the future.
“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,” Penninger 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.”