"Biochemical cigarette" against obesity
The new approach helps to reduce body weight and suppress appetite
Yulia Vorobyova, Vesti
An international team of researchers has presented a new combination therapy to combat obesity (Two-pronged approach – Novel combined therapy tackles excess fatty tissue). The treatment developed by scientists works in two directions at once: it suppresses appetite and at the same time increases energy expenditure, that is, it promotes fat burning.
Experts from the Helmholtz Center for Environmental and Health Research in Munich, who led the new study, decided to use two well-known factors affecting metabolism in the human body. And both were prompted by nature.
The first so–called weight loss factor is the effect of low temperatures. As is known, the mammalian body (including humans) has the ability to thermoregulate, that is, to maintain body temperature at the same level, regardless of the ambient temperature.
If the air temperature decreases, then a process called non-contractile thermogenesis starts in our body. We are talking about the activation of cellular metabolism – the breakdown of fat reserves to generate energy to warm the body.
However, thermogenesis also has a side effect, which is not the most useful for weight loss: with an increase in energy costs, appetite also increases. To reduce it, the new therapy uses a second "modulator" – this, oddly enough, nicotine.
It has long been known that smoking tobacco has a clear metabolic effect – it suppresses appetite. But do not worry: doctors in any case do not offer people who want to lose weight to start smoking. They only used this knowledge to find a safe alternative.
In the course of the work, experts have shown that a compound called dimethylphenylpiperazine (DMPP) stimulates the same receptors as nicotine to suppress hunger.
The new combination therapy has already passed the first preclinical trials on model animals – mice with obesity.
To trigger the activation of the so–called cold receptors – cold-sensitive ion channels called TRPM8 - the authors of the work used icilin (Icilin). It is a synthetic compound that produces the same effect as menthol: it causes a feeling of extreme cold in humans and animals. At the same time, icelin is an agonist of TRPM8 ion channels, that is, when interacting with them, it changes their state, leading to a biological response – an increase in metabolic processes.
It is important that exposure to low temperatures is not required to obtain such an effect, the scientists note. That is, full people will not have to be driven into freezers for weight loss.
During the experiments, this "treatment" stimulated the splitting of brown adipose tissue in mice. Their energy consumption increased and their body weight decreased.
However, there was no increase in appetite, since dimethylphenylpiperazine activated nicotine acetylcholine receptors in the brain of animals (more precisely, in the hypothalamus). The "inclusion" of these receptors causes a feeling of satiety, and therefore the appetite weakens, the authors explain.
It is clarified that both compounds were injected subcutaneously and in one injection to mice. The subjects received injections daily for two weeks.
It is noteworthy that during the experiments, the team noticed another positive effect: the "nicotine-like" effect not only reduced the amount of food consumed by rodents, but also significantly improved their glucose metabolism.
To compare the results, the researchers also had two control groups of mice that received monotherapy – either activation of cold-sensitive ion channels or exposure to "saturation receptors". In both cases, such treatment helped to reduce the body weight of the animals, but only slightly.
"If both [types of] treatment are combined in one therapy, then body weight and glucose metabolism improve steadily. Thus, we have gained important knowledge that can help us develop new therapeutic approaches to the treatment of obesity and diabetes," says Professor Matthias Tschöp, head of the Helmholtz Center in Munich.
Weight loss in mice with monotherapy and treatment with a combination of drugs. Black marks the results of the group that was injected with a dummy solution without active substances. A drawing from an article in Nature Communications – VM.
His team called the new strategy a "biochemical cigarette", thereby emphasizing that it is possible to get metabolic effects "like from smoking tobacco" without putting health at risk.
At the next stage, specialists will begin clinical trials of their therapy. They will have to prove the safety and effectiveness of this approach in treating people from obesity and, if necessary, adjust treatment methods.
In addition, scientists want to study in more detail the molecular interactions of various drug combinations and, possibly, find new combinations to enhance the effect of such therapy.
"Obesity is the biggest risk factor for type 2 diabetes and cardiovascular diseases. Unfortunately, diet alone is clearly insufficient to solve the ever–growing problem of obesity, so [doctors] urgently need therapeutic approaches based on drugs," concludes Matthias Chop.
His research group published an article describing the work in the journal Nature Communications (Clemmensen et al., Coordinated targeting of cold and nicotinic receptors synergistically improves obesity and type 2 diabetes).
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