When exposed to cold, clusters of cells within the body’s white fat become beige, a colour change which reflects the creation of more energy-producing mitochondria, cellular components that enable cells to burn calories and give off heat. However, as white fat cells have very few nerves, it is still unclear how beige fat cells get the message that it’s cold outside.  Now, a study from researchers at UT Southwestern Medical Center shows that the protein connexin 43 (Cx43) forms cell-to-cell communication channels on the surface of emerging beige fat cells that amplify the signals from those few nerve fibers.  The team state that their findings have implications for diabetes and other metabolic diseases.  The study is published in the journal Cell Metabolism.

Previous studies show that fat, once considered merely a storage area for excess calories, is now appreciated as a dynamic tissue that comes in several forms with different functions that are still being identified. White fat is used mainly for energy storage. Brown fat, the classic heat-generating fat, helps regulate body temperature, especially in newborns. Some white fat cells are capable of transforming into a third kind of fat, beige. Both brown and beige fat get their color from increased mitochondria that are added in response to cold and other environmental stimuli.  Several studies have shown that cold temperature can activate neurons to regulate white fat ‘beiging’.  However, white fat is traditionally known to be sparsely innervated. Details regarding the innervation and, more importantly, the propagation of the signal within the population of beige fat are sparse.  The current study shows that Cx43 gap junction channels act like conduits that speed signals across the gaps between clusters of beige and white fat cells.

The current study compared mice with Cx43 that are able to make beige fat normally to mice unable to make Cx43, meaning their white fat seldom got the message to change to beige fat in response to cold. After three weeks in cold temperatures, the mice were returned to normal temperatures and analyzed for blood sugar metabolism.  Results show that the mice which produced Cx43 show greater improvement in glucose metabolism. Data findings show, however, that both groups of animals were still able to regulate body temperature, apparently through their brown fat stores.

The lab also observed that beige fat, unlike the better-known white and brown fat, has interesting anti-diabetic effects on blood sugar metabolism that appear to be independent of temperature regulation. They note that impaired glucose metabolism is a hallmark of diabetes.  The group state that beige fat may be more interesting from an anti-diabetic, metabolic standpoint, a finding with significant clinical relevance, than from a body temperature, warming standpoint. They go on to add that, to their knowledge, this is the first time that any fat’s thermal regulatory and metabolic effects on blood sugar have been observed to work independently.

The team surmise that their findings show that Cx43 is necessary for the propagation of nerve signals that lead to beiging of white fat tissue, and how white fat cells can make maximal use of their limited number of nerves to allow a single nerve fiber to spread the ‘message’ about cold temperatures among the connected cells.  For the future, the researchers state that these findings suggest that activating Cx43 may cause the formation of more beige fat and thus increase anti-diabetic effects.

Source: UT Southwestern Medical Center