Medical

Heart disease drug reverses obesity in mice by targeting inflammation

Heart disease drug reverses obesity in mice by targeting inflammation
Fat cells might have a new foe, in the form of an already available heart disease drug that new research shows can reverse obesity in mice
Fat cells might have a new foe, in the form of an already available heart disease drug that new research shows can reverse obesity in mice
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Fat cells might have a new foe, in the form of an already available heart disease drug that new research shows can reverse obesity in mice
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Fat cells might have a new foe, in the form of an already available heart disease drug that new research shows can reverse obesity in mice
Fat cells in an obese mouse (left) and a mouse treated with digoxin (right), where improved fat burning can be observed
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Fat cells in an obese mouse (left) and a mouse treated with digoxin (right), where improved fat burning can be observed

Researchers are continuing to unravel the complex relationship between inflammation and obesity, and through a new study involving overweight mice and a repurposed heart disease drug, a group of scientists in Spain has uncovered new evidence of how the two are closely connected. The obese rodents treated with the medication experienced a 40-percent weight loss even while continuing with their unhealthy diets, and were also cured of metabolic disorders relating to the condition.

The study was carried out by scientists from The Spanish National Cancer Research Centre, who five years ago made an interesting discovery. The team was investigating the relationship between inflammation and liver cancer in mice, and saw that the mice were losing weight. The scientists suspected that a molecule called interleukin 17A, or IL-17A, which is known to trigger inflammation, could be playing a part in this, so they turned to a drug known to inhibit its activity.

The drug in question is called digoxin and is already in use as a treatment for various heart conditions, though its effects on body weight had not yet been observed. The scientists' thinking was that using the drug to suppress IL-17A activity could lead to weight loss in mice, and they've now conducted further experiments exploring that possibility.

Obese mice living on high-calorie diets were treated with digoxin, which was found to reduce their production of IL-17A. While the mice continued to be fed the unhealthy diets, they exhibited an activation of their basal metabolism, which led to the burning of excess fat and total reversal of obesity. These overweight mice soon obtained the same weight as healthy control mice on regular diets, with no negative side effects and the benefits observed for at least eight months.

Fat cells in an obese mouse (left) and a mouse treated with digoxin (right), where improved fat burning can be observed
Fat cells in an obese mouse (left) and a mouse treated with digoxin (right), where improved fat burning can be observed

"When you inhibit the production of IL-17A or the signaling pathway that this molecule activates, you don't have obesity," says Nabil Djouder, who led the research team.

According to the scientists, the experiments showed that IL-17A acts directly on fatty tissue to not just drive obesity, but lead to metabolic changes synonymous with related conditions such as type 2 diabetes, hypertension and cardiovascular disease.

"It is tempting to propose that obese patients could take digoxin for a short period until weight loss stabilizes, and then follow a healthy diet," says Ana Teijeiro, first author of the paper. "The drug could also be indicated for obesity-related pathologies, such as hypercholesterolemia, hepatic steatosis and type 2 diabetes."

While the results are promising, these effects of digoxin have only been observed in mice so far, so a lot more work is necessary to ascertain its true potential in humans. But the value of this research lies not just in the direct weight loss potential of digoxin, but the improvement in our understanding of how inflammation and obesity are connected, and how this relationship can be explored and targeted for better health outcomes.

"Thanks to this study, we know that weight loss and systemic metabolic changes are controlled by a unique molecular mechanism, IL-17A, which acts directly on adipocytes and changes their genetic profile and responsiveness to excess nutrients," Djouder says.

The research was published in the journal Nature Metabolism.

Source: The Spanish National Cancer Research Centre

6 comments
6 comments
quantumleap
Dioxin is a very dangerous drug with very limited results for heart patients. Not worth the risks, imho.
https://academic.oup.com/eurheartj/article/36/28/1831/2398087
"The present systematic review and meta-analysis of all available data sources suggest that digoxin use is associated with an increased mortality risk"
paul314
The dosage will, of course, have to be carefully calculated. Digoxin's base molecule is familiar from the foxglove plant, and has been used as a poison for millennia.
guzmanchinky
If it's already a drug used in humans, wouldn't it be easy to observe what it does in humans?
Bruce H. Anderson
How about we discontinue an unhealthy diet and shift to foods that don't cause inflammation? Pills can be helpful, but should not be the first line of defense.
Ed Clark
Quantumleap, the study you linked only looked at studies of people with atrial fibrillation (AF) and/or congestive heart failure (CHF). This is not a healthy population to begin with. I agree that caution is warranted, but there are many obese people without those two conditions.
Eggster
I recall a doctor telling me that inflammation and fatigue go hand in hand because it's the body's way of telling you to take it easy following an injury. It sounds like IL-17A is the specific trigger for this bodily response.

As for diet, the next step is to determine what foods promote IL-17A production and which ones moderate it. (Via research, not vague rules of thumb.)