Tirzepatide activates brown fat, boosting metabolism beyond appetite control

Tirzepatide is one of the drugs that has revolutionized the treatment of obesity and other conditions such as diabetes in recent years. Despite its clinical success, its precise molecular and cellular mechanisms are still not fully understood. A study in mice shows that the drug has a direct impact on improving metabolism by activating brown adipose tissue, a type of fat specialized in energy expenditure. According to the researchers, these results help to better understand the mechanisms of action of tirzepatide and open up new avenues for developing more comprehensive treatments for obesity and other metabolic diseases.

The study was led by Marion Peyrou, Ramón y Cajal researcher at the Faculty of Biology and the Institute of Biomedicine of the University of Barcelona (IBUB), the Sant Joan de Déu Research Institute (IRSJD) and the CIBER in Physiopathology of Obesity and Nutrition (CIBEROBN). 

Dual-action drug

Tirzepatide (generic name of the drug Mounjaro) is a product approved for weight control in adults with obesity or overweight with comorbidities, and also for the treatment of poorly controlled type 2 diabetes mellitus. Unlike other anti-obesity drugs, it acts simultaneously on the receptors of two hormonal factors: GIP and GLP-1. This dual action leads to significant body weight loss, mainly through reduced food intake.

To better understand how tirzepatide works, researchers conducted a comprehensive analysis of the drug's effects on different adipose tissue deposits using an experimental mouse model, as this type of analysis is not feasible in humans. First, they treated obese mice - fed a high-fat diet - with tirzepatide. The results were compared with those of a group of mice that had not received the drug but had consumed the same amount of food. This comparison made it possible to separate the effects of the drug itself from those derived solely from reduced food intake.

The results of the analysis show that tirzepatide activates brown adipose tissue, i.e. it stimulates a type of fat that specializes in 'burning' calories from food, unlike white adipose tissue, which mainly stores fat and is the type that accumulates in obesity.

This activation is associated with an increased capacity to burn metabolic energy and with the production of batokines by brown adipose tissue, molecules that are beneficial for metabolism."

Marion Peyrou, Ramón y Cajal researcher at the Faculty of Biology and the Institute of Biomedicine of the University of Barcelona (IBUB)

This finding is significant because it indicates that tirzepatide has metabolic effects beyond the weight loss it causes as a result of reducing appetite and, therefore, food intake. "This drug not only reduces body weight, but also has beneficial effects on metabolism. Active brown adipose tissue 'burns' glucose and fat within the body, which would contribute to its positive effect not only in reducing body weight, but also in lowering blood glucose and fat levels, and improving metabolism," the researcher points out.

Towards a more comprehensive treatment of obesity

The activation of brown adipose tissue has been a promising strategy for combating obesity and other metabolic disorders for years, but until now, pharmacological attempts have failed, often due to adverse side effects, especially at the cardiac level. "Tirzepatide, although it activates brown adipose tissue, does not have these negative effects; on the contrary, it shows cardiovascular benefits. If our findings are confirmed in humans, it would reinforce the importance of developing therapeutic strategies that not only reduce food intake but also increase energy expenditure and brown fat activation," explains the researcher.

This approach reinforces the idea that obesity treatments are more effective when they act simultaneously on different physiological mechanisms, thus offering a more comprehensive approach. "This could help improve weight control and reduce associated disorders, such as type 2 diabetes and other metabolic disorders," she adds.

At the same time, a more precise understanding of the mechanisms of action of tirzepatide could also help refine how these types of drugs are prescribed in the future. "Identifying which patient profiles could benefit most, for example those with more compromised energy expenditure, would open the door to more personalized medicine, based not only on appetite or weight control, but also on overall metabolic status," she emphasizes.

However, the researchers stress that we need more studies before the results of this research can be extrapolated to humans. "As this is a study conducted on mice, we must be cautious, as there may be significant differences between species in terms of metabolism regulation, adipose tissue distribution and response to drugs. Therefore, we need more clinical evidence on the action of these drugs on fat in humans," concludes Peyrou.