Why is obesity being ignored by politicians

Research team discovers gene mutation that makes people slim

It's a different kind of pandemic: people around the planet are getting fatter. In the USA, 33.7 percent of the population, including its president, are now obese and have a body mass index (BMI) of over 30. In Austria, this proportion is around 14 percent. 32 percent of Austrians - around 3.4 million - are overweight; their BMI is between 25 and 29.9.

From a medical and economic point of view, morbid overweight (obesity or obesity) is literally a serious problem for our society. A greatly increased body mass index also increases the risk of all metabolic diseases (especially type 2 diabetes mellitus), cardiovascular diseases, but also cancer. The efforts of medicine to get this epidemic under control are correspondingly great.

Genetic proportion of obesity

On the one hand, of course, it is mainly our eating habits and our movement that determine whether we weigh more or less. But there is also a genetic component of weight gain that should not be underestimated: some people tend to put on pounds more than others - regardless of their food or sports activities.

Previous studies have primarily focused on genes associated with obesity. An international team of scientists led by Josef Penninger - until 2018 scientific director at the Institute for Molecular Biotechnology (Imba) in Vienna, now head of the Life Sciences Institute at the University of British Columbia in Vancouver - has taken the opposite approach in recent years: the geneticists first investigated once the genome data of 47,102 normal-weight and extremely thin, but healthy residents of Estonia.

Mutated ALK gene in slim Estonians

As the team, to which researchers from around 20 international research institutes belonged, reported on Thursday in the renowned specialist journal "Cell", it found several genes associated with slimness in the slim Estonians, including the so-called ALK gene, which has nothing to do with alcohol , but because it encodes the protein anaplastic lymphoma kinase. This gene is already known from cancer medicine. It plays an important role in the development of lung cancer, in which, in the event of a mutation, it leads to an overproduction of ALK proteins.

For this ALK gene, Penninger's scientists have now also been able to establish a connection with other metabolic properties such as waist circumference, cholesterol level and blood sugar balance. The research for the study was far from over; it was only just beginning: In experiments with fruit flies, the removal of the ALK gene resulted in lower blood lipid levels; in experiments with mice it was found to be slim in appearance. In addition, the genetically modified animals did not gain weight despite a high-fat diet.

Hypothalamus as a switching point

Further experiments by the researchers (first author is Michael Orthofer from Imba) suggest that the place where these slimming effects occur is to be found in nerve cells in the hypothalamus, a part of the brain that is involved in hormone regulation. This is where the ALK protein evidently unfolds its slimming effect. These nerve cells regulate the energy expenditure of the fat organs via the so-called sympathetic nervous system, a part of the nervous system that is primarily responsible for activating body functions that cannot be actively influenced.

Mice in which the synthesis of the ALK protein was suppressed specifically in this area of ​​the brain had a higher fat burning rate, apparently stimulated by increased concentrations of the stress hormone norepinephrine in adipose tissue. These findings coincide with those obtained from tissue samples from thin people, which the researchers also analyzed.

Summary and assessments

"With our work we were able to prove that ALK is a completely new and essential interface in the brain that controls food utilization and the energy cycle", summarizes Josef Penninger, who is also at the forefront of the Covid 19 pandemic and whose active ingredient APN01 is currently is tested on patients. "The next important step would now be to investigate how the neurons in the hypothalamus in which ALK is active influence this metabolic control."

Some researchers who were not involved in the study were impressed by the study and the results - such as Susanne Klaus from the German Institute for Nutrition Research: "I find the amount of data overall very impressive and, as such, convincing." The metabolism expert Bernhard Paulweber from the University Hospital Salzburg has a similar view: The new findings could "open a new chapter in the search for efficient strategies to combat obesity".

Future therapy option

The big question is, of course, how and when the new research results can also be used to treat obesity. It is clear that inhibiting the ALK gene could be a new therapeutic option to prevent obesity in humans. Before this can happen, extensive research into possible effects and side effects is necessary.

By the way, one side effect is already known, at least in mice: rodents without an ALK gene tend - and this is no final gag - to excessive alcohol consumption. (Klaus Taschwer, May 21, 2020)