Researchers have discovered a new set of signals that cells send and receive to induce one type of fat cell to convert fat into heat. The signaling pathway discovered in mice has potential implications for activating the same type of thermogenic fat in humans.
Thermogenic fat cells, also called beige fat or beige adipocytes, have attracted attention in recent years due to their ability to burn energy stored as fat to help curb obesity and other metabolic disorders. Scientists have yet to turn this potential into effective therapies.
Part of the challenge of activating beige fat in humans is that this process is regulated by so-called adrenergic signals, which use the hormone catecholamine to instruct beige fat cells to burn energy. The adrenergic signal also controls other important biological functions, including blood pressure and heart rate regulation. Therefore, activation in humans with agonists has potentially dangerous side effects.
In a new study to be published online today (June 12, 2020) in the journal Developmental Cell, a team of researchers led by the University of Michigan’s Life Sciences Institute describes a pathway that prevents the thermogenesis of beige fat from being dependent on adrenergic signals can regulate. Instead, it works through a receptor protein called CHRNA2, short for Cholinergic Receptor Nicotinic Alpha 2 Subunit.
“This avenue opens a whole new direction for approaching metabolic disorders,” said Jun Wu, assistant professor at LSI and lead author on the study. “Of course, this cholinergic pathway is also involved in other important functions. So there is still a lot to be done to really find out how this could work in humans. However, these first insights are encouraging. “
For their study, Wu and her colleagues only blocked the CHRNA2 pathway in adipocytes from 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 overeating.
Wu believes the results are particularly exciting given the recent discovery by another research team of a new team of researchers that is not regulated by catecholamines. This latest study by the LSI shows that this subpopulation of beige fat, called glycolytic beige fat (or g-beige fat), can be activated via the CHRNA2 pathway.
“Many patients with metabolic disorders have catecholamine resistance, which means their cells do not recognize or respond to catecholamines,” said Wu, who is also an assistant professor of molecular and integrative physiology at UM Medical School.
“Even if it could be done safely, activating this adrenergic pathway would not be an effective treatment option for such patients. This new avenue with this new subtype of beige fat could be the start of a whole new chapter to address that challenge. “
Reference: “Adrenergic-independent signal transmission via CHRNA2 regulates the activation of beige fat” by Heejin Jun, Yingxu Ma, Yong Chen, Jianke Gong, Shanshan Liu, Jine Wang, Alexander J. Knights, Xiaona Qiao, Margo P. Emont, XZ Shawn Xu, Shingo Kajimura, and Jun Wu, June 12, 2020, Development Cell.
DOI: 10.1016 / j.devcel.2020.05.017
The research was supported by the National Institutes of Health, the American Diabetes Association, the Chinese Scholarship Council, and the Michigan Life Sciences Fellows program.
The study’s authors are: Heejin Jun, Shanshan Liu, Jine Wang, Alexander Knights, Margot Emont, XZ Shawn Xu, and Jun Wu from UM; Yingxu Ma from UM and Central South University, China; Yong Chen and Shingo Kajimura from the University of California at San Francisco; Jianke Gong from UM and Huazhong University of Science and Technology; and Xiaona Qiao from UM and Fudan University, China.