Researchers identify a new approach to turning on the heat in energy-burning fat cells

Researchers have discovered a new set of signals that cells send and receive to prompt one type of fat cells to convert fat into heat. The signaling pathway, discovered in mice, has potential implications for activating this same type of thermogenic fat in humans. 

Thermogenic fat cells, also called beige fat or beige adipocytes, have gained considerable attention in recent years for their potential to curb obesity and other metabolic disorders, due to their ability to burn energy stored as fat. But scientists have yet to translate this potential into effective therapies.

The challenge of activating beige fat in humans arises, in part, because this process is regulated through so-called adrenergic signaling, which uses the hormone catecholamine to instruct beige fat cells to start burning energy. But adrenergic signaling also controls other important biological functions, including blood pressure and heartbeat regulation, so activating it in humans with agonists has potentially dangerous side effects.

In a new study published online June 12 in the journal Developmental Cell, a team of researchers led by the University of Michigan Life Sciences Institute describes a pathway that can regulate beige fat thermogenesis independently of adrenergic signaling. Instead, it operates through a receptor protein called CHRNA2 (short for Cholinergic Receptor Nicotinic Alpha 2 Subunit).

“This pathway opens a whole new direction for approaching metabolic disorders,” says Jun Wu, Ph.D., an assistant professor at the LSI and the study’s senior author. “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.”