Experts at the University of Michigan are one step closer to developing ways to boost the body’s natural metabolic response. The researchers have identified a signaling pathway that triggers fat burning in thermogenic fat cells.
In recent years, scientists have been exploring ways to activate thermogenic fat cells, or beige fat, due to their ability to burn fat. Targeting these cells could help treat obesity and other metabolic disorders, but activating beige fat in humans presents challenges.
A process called adrenergic signaling uses the hormone catecholamine to instruct beige fat cells to start burning energy. However, adrenergic signaling also regulates other important biological functions, such as blood pressure and heartbeat, so controlling this process in humans has the potential for dangerous side effects.
In the new study, researchers have discovered a pathway that can regulate beige fat thermogenesis independently of adrenergic signaling. The pathway utilizes a receptor protein called Cholinergic Receptor Nicotinic Alpha 2 Subunit (CHRNA2).
Study senior author Jun Wu is an assistant professor at the University of Michigan Life Sciences Institute (LSI).
“This pathway opens a whole new direction for approaching metabolic disorders,” said Professor Wu. “Of course, this cholinergic pathway also is involved in other important functions, so there is still much work to do to really figure out how this might work in humans. But we are encouraged by these initial findings.”
To investigate, the team blocked the CHRNA2 pathway in the beige fat of mice, and then fed them a high-fat diet. Without the CHRNA2 receptor proteins, the mice gained more weight and were less able to activate thermogenesis and burn fat.
According to Professor Wu, the findings are particularly exciting in light of the recent discovery of a new type of beige fat – glycolytic beige fat – that is not regulated by catecholamine. The LSI study indicates that glycolytic beige fat can be activated through the CHRNA2 pathway.
“Many patients with metabolic disorders have catecholamine resistance, meaning their cells do not detect or respond to catecholamine,” said Professor Wu. “So even if it could be done safely, activating that adrenergic pathway would not be an effective treatment option for such patients. This new pathway, with this new subtype of beige fat, could be the beginning of a whole new chapter for approaching this challenge.”
The study is published in the journal Developmental Cell.