Research reveals visceral mechanism of brown fat and potential for obesity treatment

Brown fat, also known as brown adipose tissue (BAT), is a type of fat in the body that is different from the white fat we are familiar with around the abdomen and thighs. Brown fat has a special function, helping us convert calories from the food we eat into heat, especially when we are exposed to cold temperatures, such as during winter swimming or cryotherapy. For a long time, scientists thought that only small animals, such as mice and newborn babies, had brown fat. However, new research shows that a certain number of adults retain brown fat throughout their lives. Brown fat is so good at burning calories that scientists are trying to find ways to safely activate it using drugs that increase its ability to generate heat.

A new study by Professor Jan-Wilhelm Kornfeldt of the University of Southern Denmark/Novo Nordisk Adipocyte Signaling Center (Adiposign) and the research group of Dagmar Wachten of the University Hospital Bonn and the University of Bonn (Germany) shows that brown fat has the ability to It incorporates a previously unknown mechanism that switches off brown fat immediately after it has been converted. This limits its effectiveness as a treatment for obesity. Hande Topel, lead author of the study and a senior postdoctoral researcher at the University of Southern Denmark and the Novo Nordisk Adipocyte Signaling Center (AdipoSign), said the research team has now identified proteins involved in this switch-off process. It is said that he discovered. It's called “AC3-AT.”

Blocking the “off switch” opens up new strategies

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

Hande Topel, Senior Postdoctoral Researcher, University of Southern Denmark

The research team discovered the switch-off protein using advanced techniques to predict unknown proteins. Dr. Hande Topel explains: “When we studied mice that did not genetically have AC3-AT, we found that their bodies were simply better at burning calories and were able to increase their metabolic rate by activating it, which protected them from obesity. Brown fat.

When two groups of mice were fed a high-fat diet for 15 weeks, the mice became obese. The AC3-AT protein-depleted group gained less weight and was metabolically healthier than the control group. “Mice lacking the AC3-AT protein had less fat accumulation and increased lean body mass compared to control mice,” said co-author Ronja Cardinal, a PhD student at the University of Bonn. Says. Dagmar Wachten's lab at UKB continued: “AC3-AT is found not only in mice but also in humans and other species, so it has direct therapeutic implications for humans.”

Expectations for strategies that support weight loss

Although the prevalence of brown fat decreases as humans age, and brown fat in adults is not as abundant as in newborns, it can still be activated, such as by cold exposure. When activated, this increases metabolic rate in these people and may help stabilize weight loss even in situations where calorie intake is (too high).

Interestingly, this study not only identified a shorter, previously unknown form of the AC3 protein, AC3-AT. Researchers also identified other unknown protein/gene versions that respond to cold exposure, similar to AC3-AT.

“However, further research is needed to elucidate the therapeutic efficacy of these alternative gene products and their regulatory mechanisms upon BAT activation,” said co-corresponding author and co-director of the UK Institute of Innate Immunity. Professor Dagmar Wachten, a fellow member, said: Researcher in the Cluster of Excellence ImmunoSensation2 and the Transdisciplinary Research Area (TRA) “Modeling'' and “Life & Health'' at the University of Bonn.

“Understanding this type of molecular mechanism not only sheds light on the regulation of brown fat, but also has the potential to elucidate similar mechanisms in other cellular pathways. This could help advance our understanding and develop new treatments,'' says co-author Professor Jan Wilhelm Kornfeld of the University of Southern Denmark.

This study was carried out in the context of the DFG Collaborative Research Center Transregio-SFB 333 “Brown and beige fat – organ interactions, signal transduction pathways, and energy balance (BATenergy)”. This study aims to improve our understanding of different types of adipose tissue and adipose tissue. Research at the Novo Nordisk Foundation Adipocyte Signaling Center (AdipoSign) at the University of Southern Denmark aims to understand the role of adipocytes in metabolic diseases and their dysfunction in model organisms and obese patients. It is being said.