BOSTON—Researchers at the Joslin Diabetes Center have identified two molecular pathways that lead to a protein called necdin that blocks brown fat growth. The findings, published in the journal Endocrinology, suggest the discovery may one day play a role in obesity and diabetes prevention.
The researchers sought to find out more about how to get brown fat cells to grow because brown fat actually burns energy rather than storing it like the more common white fat. The discovery allows the researchers to look for ways to modify the steps along the pathways, either to stimulate another protein, called CREB, which shuts down necdin, or block a different protein called FoxO1, located along the second pathway, which stimulates necdin. The study showed for the first time that the two proteins can bind directly to the necdin gene.
"This is a very important piece of the puzzle," the researchers said. "It provides new opportunities. The point is that we have got to learn how to grow these brown fat cells. There's a lot of missing information. We filled in some of the important missing pieces."
For the study, the researchers conducted tests in vitro on different cell lines derived from brown fat taken from mice. They used different drugs to stimulate or block the signaling pathways they thought were important. The result was they defined the two pathways. One pathway to necdin starts with insulin cells and runs through proteins called Ras and ERK1/2 before getting to CREB. The second also starts with insulin and runs through proteins called P13-K and Akt before getting to FoxO1.
"With this more detailed description of the pathways leading to (brown fat tissue), there can be more focused attempts to develop interventions using brown fat as a treatment for obesity and diabetes," the researchers said.
