From the heart and obesity
It is known that obesity is an inflammatory disease, that is, a chronic protective reaction of the body to stress caused by an excess of nutrients. Based on this approach, a group of researchers led by Nabil Juder from the Spanish National Cancer Research Center (CNIO) tried to cure obesity by preventing inflammation. Their article, published in the journal Nature Metabolism, shows that the drug digoxin, already used in various heart diseases, reduces inflammation and leads to a 40% reduction in body weight in mice without any side effects. Digoxin also relieved the animals of metabolic disorders associated with obesity.
Pro-inflammatory molecule as a cause of obesity
Digoxin reduces the production of the pro-inflammatory cytokine interleukin 17A (IL-17A). The researchers identified IL-17A as a causal factor of obesity: inhibition of IL-17A synthesis or the signaling pathway that this molecule activates led to normalization of body weight.
They found that IL-17A acts directly on adipose tissue, causing severe metabolic changes associated with weight gain – the so-called metabolic syndrome, which includes type 2 diabetes, hypertension and cardiovascular diseases.
Digoxin activates metabolism
Animals with alimentary obesity continued to eat the same high–calorie food as before, however, against the background of digoxin, they showed activation of basal metabolism - metabolism for generating energy needed by the body at rest to perform basic functions (respiration, blood circulation, etc.). Activation of basal metabolism led to burning excess fat and weight loss.
The researchers followed the mice for several weeks and did not find any side effects of digoxin. The effects persisted for at least eight months, which proves that resistance mechanisms do not develop.
Adipocytes of obese mice (left) and after digoxin treatment (right).
If the treatment shows the same effectiveness in humans, then obese patients will be able to take digoxin for a short period of time until the weight normalizes, and then adhere to a healthy diet. The drug can also be indicated for pathologies associated with obesity, such as hypercholesterolemia, liver steatosis and type 2 diabetes mellitus.
Epidemiological and clinical studies are needed to confirm the results.
The first causal relationship between obesity and inflammation
In addition to this potential clinical significance, the study proved a causal relationship between inflammation and pathological weight gain: IL-17A acts directly on adipocytes and alters their genetic profile and response to excess nutrients. This opens up new possibilities for investigating the molecular mechanisms that make obesity an inflammatory disease. Understanding the relationship between excess nutrients, inflammation and obesity is necessary to find new approaches to the treatment of metabolic disorders.
The increase in the prevalence of obesity
Overweight is a serious global health problem and affects 1.9 billion adults, of which 600 million people are obese. According to some forecasts, half of the world's population will be obese within the next decade. To date, it has no effective treatment. Therapy based on lifestyle changes – changes in diet and physical activity – allows you to reduce weight by about 10%, and drugs aimed at reducing appetite or removing fat lead to a loss of body weight from 2% to 7%.
This study provides a promising new strategy: fighting obesity by disabling its inflammatory component.
Available drug
Digoxin has long been used to treat heart failure, and it has been known to act on IL-17A. Its effect on body weight, however, has never been studied. Jouder explains this by saying that cardiovascular diseases cause fluid retention, which masks the effect of weight loss in patients taking digoxin.
Thus, digoxin, any of its derivatives, or other IL-17A inhibitors can be very effective means of combating obesity and metabolic diseases. They should be evaluated in clinical trials.
Article by A.Teijeiro et al. Inhibition of the IL-17A axis in adipocytes suppresses diet-induced obesity and metabolic disorders in mice is published in the journal Nature Metabolism.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on CNIO materials: CNIO researchers discover that a drug already in use in humans corrects obesity in mice, with no side effects.