Zepbound and Mounjaro may turn on the body’s calorie-burning brown fat

According to the researchers, the findings provide new clues about how tirzepatide works and could help guide the development of broader treatments for obesity and other metabolic disorders.

The research 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).

Tirzepatide Targets Two Hormone Receptors

Tirzepatide (generic name of the drug Mounjaro) is approved for weight management in adults with obesity or overweight with comorbidities, as well as for treating poorly controlled type 2 diabetes mellitus.

Unlike some other obesity medications, tirzepatide targets the receptors for two hormonal factors at the same time: GIP and GLP-1. This dual mechanism can produce substantial weight loss, largely because the drug reduces food intake.

Researchers wanted to determine whether tirzepatide also produces metabolic changes that cannot be explained simply by eating less.

To investigate, the team examined how the drug affected different fat deposits in an experimental mouse model, since this kind of detailed tissue analysis cannot readily be performed in humans. Obese mice -- fed a high-fat diet -- were treated with tirzepatide.

The researchers then compared those animals with mice that did not receive the drug but were given the same amount of food. By controlling food intake this way, the scientists could distinguish changes caused directly by tirzepatide from those resulting from reduced calorie consumption.

Mounjaro Activates Calorie-Burning Brown Fat

The analysis showed that tirzepatide activated brown adipose tissue. Unlike white adipose tissue, which primarily stores fat and tends to accumulate in obesity, brown fat specializes in using energy and 'burning' calories from food.

"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," says Marion Peyrou.

The finding suggests that tirzepatide may influence metabolism in ways that extend beyond the weight loss caused by appetite suppression and reduced 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.

A Broader Strategy for Treating Obesity

Scientists have long viewed brown fat activation as a potentially useful strategy for treating obesity and other metabolic diseases. However, previous efforts to activate brown adipose tissue with drugs have often been unsuccessful because of unwanted side effects, particularly those affecting the heart.

"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.

The results support the idea that obesity therapies may be more effective when they target several physiological processes at once instead of focusing only on appetite.

"This could help improve weight control and reduce associated disorders, such as type 2 diabetes and other metabolic disorders," she adds.

Toward More Personalized Obesity Treatment

A clearer picture of how tirzepatide works could also influence how drugs in this class 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.

The researchers caution, however, that the findings come from mice and cannot yet be assumed to apply in the same way to people. Human and mouse metabolism can differ substantially, as can the distribution of fat tissue and responses to medications.

"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.