We are all familiar with the concept of the Freshman Fifteen. Thanks to academic stressors and buffet-style cafeterias, the first year of college is nearly synonymous with weight gain. Even at Hopkins, most students put on a few pounds in the first couple of months.
While the Freshman Fifteen rarely signals more than a modest weight gain, many people in the U.S. experience significant weight gains throughout the course of their lives. Adding too much weight can be medically risky, as excess body weight is known to cause a variety of medical complications, including diabetes and fatty liver disease. However, the molecular mechanism behind this correlation has proven to be somewhat elusive. Nevertheless, a team of Hopkins researchers thinks it has found an explanation: in a recently published report, this team presented a molecular switch that may alleviate fat-induced diseases.
The proposed switch regulates the process of cellular fat production in cells. This process, which involves several convoluted pathways, is necessary for cellular operations and maintenance. Fats, despite the prevailing attitude of low-fat dieters, are indispensable to our bodies. However, if cellular fat levels are too high, the liver starts undergoing a process called liver scarring in which liver cells are replaced by fat cells. This cellular replacement reduces the liver’s ability to process toxins and hormones, setting the body in disarray.
In order to maintain an adequate level of fat in cells, our body produces sterol regulatory element-binding proteins (SREBPs). These proteins, which are found on the membrane of the endoplasmic reticulum in cells, must be transported to the nucleus in order to effect cellular change. To allow for this movement, the proteins must be cut from the membrane by two proteins called S1P and S2P. The Hopkins research team found a protein called SCAP that is responsible for moving SREBPs towards S1P and S2P, thereby allowing SREBP to be cut from the membrane.
According to the recent paper, SCAP is constantly made within the endoplasmic reticulum but immediately destroyed once it leaves that organelle. Interestingly, SCAP breakdown is dependent on S1P function. In engineered cells, the Hopkins researchers demonstrated that SCAP is only broken down if S1P is active.
Even though there are no immediate medical applications for this discovery, it is a crucial step in developing our understanding of fat accumulation in cells. Because SCAP interacts with factors known to influence cellular fat regulation, a better understanding of this molecule may help scientists develop treatments for obesity and its related diseases.
