Scientists Discover “Off Switch” Protein That Limits Brown Fat’s Calorie-Burning Potential

Researchers from the University of Southern Denmark, the Novo Nordisk Center for Adipocyte Signaling (Adiposign), and the University of Bonn have identified a protein called ‘AC3-AT’ that acts as an “off switch” for brown fat, limiting its effectiveness in burning calories and combating obesity. This discovery opens up new possibilities for developing targeted therapies to tackle obesity and related health problems.

The Unique Role of Brown Fat

Brown fat, also known as brown adipose tissue (BAT), is a special type of fat that burns calories from the foods we eat, converting them into heat. This process is particularly helpful when we’re exposed to cold temperatures. While it was once thought that only small animals and newborns possessed brown fat, recent research has shown that some adults maintain it throughout their lives. Scientists are now exploring ways to safely activate brown fat using drugs that boost its heat-producing abilities to combat obesity.

“Looking ahead, we think that finding ways to block AC3-AT could be a promising strategy for safely activating brown fat and tackling obesity and related health problems,” says Hande Topel, Senior Postdoc at the University of Southern Denmark and the Novo Nordisk Center for Adipocyte Signaling (Adiposign).

Promising Results in Mice Studies

The research team conducted a study on two groups of mice fed a high-fat diet for 15 weeks, rendering them obese. The group that had their AC3-AT protein removed gained less weight than the control group and were metabolically healthier. They also accumulated less fat in their body and increased their lean mass compared to the control mice.

“As AC3-AT is found not only in mice but also in humans and other species, there are direct therapeutic implications for humans,” says co-author Ronja Kardinal, a PhD student at the University of Bonn.

The study not only identified AC3-AT but also other unknown protein/gene versions that respond to cold exposure, similar to AC3-AT. Further research is needed to understand the therapeutic impact of these alternative gene products and their regulatory mechanisms during brown fat activation.

“Understanding these kinds of molecular mechanisms not only sheds light on the regulation of brown fat but also holds promise for unraveling similar mechanisms in other cellular pathways. This knowledge can be instrumental in advancing our understanding of various diseases and in the development of novel treatments,” says co-corresponding author Prof. Jan-Wilhelm Kornfeld from the University of Southern Denmark.

Sajjad Khani, Hande Topel, Ronja Kardinal et al; Cold-induced expression of a truncated Adenylyl Cyclase 3 acts as rheostat to brown fat function; Nature Metabolism;
DOI: 10.1038/s42255

Keyword/phrase: brown fat off switch protein



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