Already known in cancer research, the ALK gene appears to influence a person’s thinness. Discovery by Austrian scientists may provide possible therapeutic approaches to obesity. In order to investigate the possible genetic causes of a slim figure, researchers led by Josef Penninger of the Vienna Institute of Molecular Biotechnology (IMBA), examined the genome data of a group Estonian population of thin and healthy people, with a very low body mass index (BMI).

ALK gene is also linked to waist size, cholesterol and blood sugar levels, scientists say

Photo: DW / Deutsche Welle

They found several genes that are associated with slender body volume – including the ALK gene (anaplastic lymphoma kinase). Their results were published in the specialized magazine Cell.

For the ALK gene, the researchers were also able to determine a connection with other metabolic properties, such as waist size, cholesterol and blood sugar levels.

In other experiments with flies, the removal of the ALK gene resulted in lower levels of lipids in the blood and in mice, similar in appearance to slim people. In addition, genetically modified animals have not gained weight, despite foods high in fat.

Subsequent studies with rats suggested that the site of origin of these slimming effects can be found in the nerve cells of the hypothalamus – the region of the brain involved in hormonal regulation. There, the ALK protein apparently reveals its slimming effect.

The mice that suppressed ALK protein synthesis specifically in that region of the brain had a higher fat burning rate. This was apparently stimulated by an increased concentration of the norepinephrine stress hormone in adipose tissue. These results coincide with those from tissue samples from thin people, which the scientists also analyzed.

This new research is particularly interesting for other researchers, because Viennese scientists have chosen a completely new approach. “In this context, the present study follows a new and interesting path, not focusing on the genes of obesity, but on the genes that are associated with slimness in humans,” said Stephan Herzig, scientific director of the Helmholtz Diabetes Center in Munich.

Research on weight control also focuses on overweight and obesity, according to Bernhard Paulweber, head of the Department of Metabolic Diseases and Medical Molecular Biology at Salzburg University Hospital. Here the reverse path was followed.

“The elucidation of these mechanisms may open a new chapter in the search for efficient strategies to combat overweight, obesity and associated disorders, especially type 2 diabetes,” said Paulweber.

Can the results be applied to humans?

The ALK gene is already known in oncology. There, it is considered an important conducting gene in the development of lung cancer, where in the case of a mutation it leads to an overproduction of ALK proteins.

ALK inhibitors, which suppress the function of ALK proteins, are used as medicines. The results of the research by Penninger and his team now raise the question of whether these drugs can also be used to treat obesity.

Like his other scientific colleagues, Paulweber also has reservations about the application of knowledge acquired in human beings.

“The beneficial effects of turning off the ALK gene shown in the animal model are not directly transferable to humans. Many studies are still needed to find ways to make these results useful in the therapy of obesity and associated disorders in humans,” concluded Paulweber.


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Deutsche Welle
Deutsche Welle is Germany’s international broadcaster and produces independent journalism in 30 languages.