Study reveals brown fat’s built-in mechanism and potential obesity treatment

Brown fat, also known as brown adipose tissue (BAT), is a type of fat in our bodies that is different from the white fat around our bellies and thighs that we are more familiar with. Brown fat has a special job—it helps burn calories from foods we eat in the heat, which can be helpful, especially when we’re exposed to cold temperatures like during winter swimming or cryotherapy. For a long time, scientists believed that only small animals like mice and newborns had brown fat. But new research shows that a certain number of adults retain their brown fat throughout life. Because brown fat is so good at burning calories, scientists are trying to find ways to safely activate it by using drugs that boost its heat-generating abilities.

A new study by the research groups of Professor Jan-Wilhelm Kornfeld from the University of Southern Denmark/Novo Nordisk Center for Adipocyte Signaling (Adiposign) and Dagmar Wachten from the University Hospital of Bonn and the University of Bonn (Germany) found that Brown fat has an unknown built-in mechanism that deactivates it shortly after it is activated. This limits its effectiveness as an anti-obesity treatment. According to the study’s first author, Hande Topel, who is a Senior Postdoc at the University of Southern Denmark and the Novo Nordisk Center for Adipocyte Signaling (Adiposign), the team has now discovered a protein responsible for this deactivation process. It is called ‘AC3-AT’.

Blocking the “off switch” opens up a new strategy

Looking ahead, we believe that finding ways to block AC3-AT could be a promising strategy to safely activate brown fat and treat obesity and related health problems.”

Hande Topel, Senior Postdoc, University of Southern Denmark

The research team found the deactivation protein using advanced technology that predicts unknown proteins. Hande Topel explains: “When we studied mice that genetically lacked AC3-AT, we found that they were protected from becoming obese, in part because their bodies were simply better at burning calories and were able to increase their metabolic rates through of brown fat activation’.

Two groups of mice were fed a high-fat diet for 15 weeks, which made them obese. The group in which the AC3-AT protein was removed gained less weight than the control group and was metabolically healthier. “Mice lacking the AC3-AT protein also accumulated less body fat and increased their lean mass compared to control mice,” says co-author Ronja Kardinal, who is a PhD student at the University of Bonn. in Dagmar Wachten’s lab at UKB, continuing: “As AC3-AT is found not only in mice but also in humans and other species, there are direct therapeutic implications for humans.”

We hope for strategies that support weight loss

Although the prevalence of brown fat decreases as people age, and despite the fact that adults do not have as much brown fat as newborns, it can still be activated, for example by exposure to cold. When activated, it boosts the metabolic rate of these individuals, which again can help stabilize weight loss in conditions where calorie intake is (too) high.

Interestingly, this study not only identified AC3-AT, which is a shorter, previously unknown form of the AC3 protein. The researchers also identified other unknown cold-responsive protein/gene versions similar to AC3-AT.

“However, further research is needed to elucidate the therapeutic impact of these alternative gene products and their regulatory mechanisms during BAT activation,” says co-corresponding author Prof. Dagmar Wachten, Co-Director of the Institute of Innate Immunity at UKB and member of Cluster of Excellence ImmunoSensation2 and the Interdisciplinary Research Areas (TRA) ‘Modelling’ and ‘Life & Health’ at the University of Bonn.

“Understanding these kinds of molecular mechanisms not only sheds light on the regulation of brown fat, but also holds promise for uncovering similar mechanisms in other cellular pathways. This knowledge can help advance our understanding of various diseases and develop new treatments.” ” , says co-corresponding author Professor Jan-Wilhelm Kornfeld, University of Southern Denmark.

This study was conducted within the DFG Collaborative Research Center Transregio-SFB 333 “Brown and Beige Fat – Organ Interactions, Signaling Pathways and Energy Balance (BATenergy)”, which seeks to better understand the different types of adipose tissue and their role in metabolic diseases and the Novo Nordisk Foundation Center for Adipocyte Signaling (Adiposign) at the University of Southern Denmark which aims to understand adipocyte dysfunction in model organisms and obese patients.