Researchers at the University of Michigan in Ann Arbor have discovered a new set of signals that cells send and receive to prompt a type of fat cell to convert fat into heat.
Thermogenic fat cells, also called beige fat or beige adipocytes, have gained attention in recent years for their potential to curb obesity and other metabolic disorders due to their ability to burn energy stored as fat.
The signaling pathway was discovered in mice and has potential implications for activating the same type of thermogenic fat in humans.
But there has been a challenge with the process. It is regulated through adrenergic signaling, which uses the hormone catecholamine to instruct beige fat cells to start burning energy. However, adrenergic signaling also controls other biological functions including blood pressure and heartbeat regulation, potentially creating dangerous side effects.
In a study published online on June 12 in the journal Developmental Cell, a team of researchers led by the U-M Life Sciences Institute describes a pathway that can regulate beige fat thermogenesis independently of adrenergic signaling. Instead, it operates through a receptor protein called Cholinergic Receptor Nicotinic Alpha 2 Subunit (CHRNA2).
“This pathway opens a whole new direction for approaching metabolic disorders,” says Jun Wu, an assistant professor at the institute 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.”
Wu and her colleagues blocked the CHRNA2 pathway only in adipocytes in mice and then fed the mice a high-fat diet. Without the CHRNA2 receptor proteins, the mice showed greater weight gain than normal mice and were less able to activate thermogenesis in response to excess food intake.
Another research team unaffiliated with U-M discovered a new type of beige fat that is not regulated by catecholamine. This newest study from U-M indicates that this subpopulation of beige fat, called 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,” says Wu, who is also an assistant professor of molecular and integrative physiology at the U-M Medical School. “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 research was supported by the National Institutes of Health, American Diabetes Association, Chinese Scholarship Council, and Michigan Life Sciences Fellows program.
