a Team of scientists led by Michael Orthofer from the Institute of molecular biotechnology at the Austrian Academy of Sciences (IMBA) analyzed genetic database of the Estonian Biobank, which has 47 102 “metabolically healthy lean” of a person aged 20 to 44 years. The task was to identify the gene of “thinness”. The results are published in the journal Cell.
“This gene is approximately 1% of the population,” says lead author Joseph Penninger. They can eat a lot and whatever I want, and not gain weight”.
For these lucky ones the harmony is not the result of proper nutrition, sports or “regular squats”, but a genetic given.
“Many people study obesity and genetics, said Penninger. We decided to study thinness”.
the Estonian Biobank has proved ideal for study because it presents a broad age range and information about the phenotype. The scientists compared the DNA samples and clinical data of healthy thin people, whose body mass index in the long term was below 18 (corresponding to reduced weight), with data from study participants with normal or overweight.
the Result was impressive: it was discovered a genetic variation that is unique to lean people, a mutation in the gene ALK (anaplastic lymphoma kinase gene anaplastic lymphoma kinase). It was found that the inhibition of the synthesis of ALK gene increases the rate of fat burning and ensures that maintaining a low body weight.
Science is known that the ALK gene is frequently mutated in several types of cancer, such as lung cancer and neuroblastoma. “ALK have been studied extensively in the context of cancer, but outside this context on the biological role of this gene, little is known,” says Orthofer.
As shown by the work, a partial sequence of the gene ALK was disproportionately deactivated in very thin study participants. This suggests that the ALK gene can affect the metabolism and body weight.
the researchers conducted additional experiments with mice. They are specifically deactivated the ALK gene in some animals, and from birth they were fed a normal diet. When the mice with the deleted ALK increased, it was found that their weight and body fat percentage was significantly lower than in rodents from the control group, although the mice with the deleted gene ALK ate the same as their peers, and the same move. This effect was even more pronounced when the diet is high in fat: in a few weeks, according to the researchers, the difference in body fat was 50%. A more thorough analysis showed that the blocking of ALK gene in mice leads to an increase in free fatty acids in blood plasma, indicating increased fat burning. In addition, the researchers also found evidence that the fat tissue in animals thickets�� detected by the hormone noradrenaline, which is important for fat metabolism.
According to Orthofer, these results indicate that the ALK gene plays an important role in the metabolism and that its deactivation promotes the burning of fat: “That’s why the animals remain lean even with a diet high in fat”.
However, as shown by further investigation, disabling of this gene in the adipose tissues, liver or in the immune system had no changes on weight of rodents. “However, when we specifically deactivated in the ALK region of the hypothalamus, we observed a similar reduction in weight, as in animals, in which ALK has been disabled throughout the body, – says Orthofer. – This is interesting because the hypothalamus is the Central point of coordination of metabolism and regulates fat burning through norepinephrine”.
According to the authors, the discovery could help develop new drugs against obesity. “Our study shows that the gene ALK, which is expressed in the brain, responsible for regulation of metabolism and energy expenditure, concludes Penninger. – Inhibition of the gene ALK could be a new therapeutic option for the prevention of obesity”.
