Some people diet to stay in shape and spend long hours in the gym, while others can stay fit effortlessly, no matter what they eat. In a study published in the journal Cell on May 21, researchers used a database of genetic material of more than 47,000 people in Estonia to effortlessly identify people who are weak. against weight gain They tried to determine whether the resistance was attached to the gene.
In studies on organisms, it has been observed that if the gene is deleted, flies and mice are weaker and the expression of the gene plays a role in the regulation of energy consumption in the brain.
Senior author Josef Penninger, professor of medical genetics at the British Columbia University and director of the Life Sciences Institute,
“We all know these people who make up one percent of the society,” he says.
“They can consume whatever they want, in the amount they want, with their healthy metabolism. Moreover, they do not have to exercise constantly to avoid gaining weight. ”
“Obesity and obesity genetics has always been a popular topic. We thought of approaching the subject a little differently. We said, ‘Let’s take it backwards,’ and decided to work on weakness. ”
Penninger’s team evaluated data from 47,102 people aged 20 to 44 in Estonia’s biobank. The researchers compared the DNA samples and clinical data of healthy and lean people with those of normal weight, and as a result, they discovered a genetic change in the ALK gene of lean people.
The ALK gene is known for its continuous mutions in various types of cancer. In addition, ALK has been recognized as an oncogene involved in tumor formation. The function of ALK other than cancer was not known until now, but with the presence of new findings, ALK can be considered a specific weakness gene with its resistant attitude to weight gain.
Researchers also found that flies and mice lacking the ALK gene maintained weakness and gained resistance to dietary obesity. Moreover, normal mice with the same diet and level of physical activity Compared to mice with the ALK gene deleted, mice with the ALK deleted had less weight and less body fat.
At the same time, studies in mice indicated that the ALK gene, which is highly expressed in the brain, preferred fat stored in tissues during fat burning rather than dietary fat.
ALK, a Targetable Gene
Researchers predict that by targeting the ALK gene therapeutically, success can be achieved in the fight against obesity in the coming years. “If we think about it, we can turn off the ALK gene and reduce the function of the gene to see if we will remain weak,” says Penninger. “ALK suppressors have already been used in cancer treatments.
ALK is a targetable gene. It is possible that we can inhibit the activity of ALK, and we will definitely try it in the coming years. ” Of course, more studies are needed for this purpose to see how effective the suppressors are.
In addition, the researchers plan to investigate how neurons expressing the ALK gene regulate the brain at the molecular level, balance metabolism, and promote weakness.
The Estonian Biobank is a convenient database for researchers, with a wide age range and strong phenotypic data. Repeating the findings is the only limiting factor of the database used. Because biobanks that collect biological or medical data and tissue samples do not have a universal standard for data collection. This is a situation that makes comparison difficult. The researchers report that they should verify their findings with other data banks using the method of batch analysis. “You learn a lot from biobanks,” says Penninger. “But like everything else, this is not a final answer to life. But these are pretty good starting points for validation, important links and formations regarding human health. The researchers state that this research is unique, as the basis of the weakness in society – the genome – and the function of the gene of interest was discovered in vivo (testing on organisms) through analysis on flies and mice.
“Bringing together diverse groups, from nutrition to biobanking to demanding mouse and fly genetics, is a great job,” says Penninger. “However, this is a solid biochemistry and genetics story that includes evolutionary trees in metabolism, the evolutionary role of ALK, human evidence, to provide causal evidence.”