Now, new research has identified a gene that could play a role. Its name is ALK (Anaplastic Lymphoma Kinase), and mutations in this gene have already been linked to certain cancers and identified as engines of tumor growth.
The latest study found two particular ALK variations that appear in thin, low-BMI individuals – but not in normal-weight individuals. The analysis focused on the DNA of 47,102 people aged 20 to 44, extracted from the Estonian “biobank”, a biological database collected from a large percentage of the Estonian population.
“We wanted to understand why,” said medical geneticist Josef Penninger from the University of British Columbia in Canada. “Most researchers are studying obesity and the genetics of obesity. We just reversed it and studied thinness, opening up a new area of research. “
In follow-up tests on mice and Drosophila fruit flies, animals that had the ALK gene turned off, remained thinner than normal – even when the mice were fed what researchers described to CNN as “a McDonald’s diet”.
Other tests have shown that mice without the ALK gene had lower than normal body weight and body fat levels.
Of course, the correlation is not causation. But the researchers suggest that the gene, which is highly expressed in the brain, plays a role in telling the body how much fat to burn and how to use its energy stores.
Yet, for now, all we’ve shown is that this direct link exists in fruit flies and mice, not humans. Despite extensive research into the implication of the gene in cancer, our understanding of the role of the ALK gene in human physiology remains largely unclear.
But a promising aspect of the discovery is that scientists already know how to inhibit ALK in humans due to its role in the development of cancer, so it is possible to test the link further.
“If you think about it, it’s realistic that we can stop ALK and reduce the ALK function to see if we stayed skinny,” says Penninger.
“ALK inhibitors are already used in cancer treatments. He can be targeted. We could possibly inhibit ALK, and we will try to do so in the future. “
Other studies will also need to take a closer look at how the ALK gene works in the brain: how it potentially balances metabolism and leads to leaner body shape at the molecular level.
Even if a clear link between ALK mutations and resistance to weight gain is established, it is likely to be only part of a much broader set of genetic factors – as suggested by previous research.
Although biobank data and tests on mice and flies are a good starting point to solve the mystery link between genetics and thinness, scientists will need much more data in the future before they can understand what’s really going on here.
“You learn a lot from biobanks,” says Penninger. “But, like everything, it is not the ultimate answer to life, but these are the starting points and very good confirmation points, very important links and associations for human health. “
The research was published in Cell.