Fat Storage and the Discovery of Lipid Droplets: How Understanding “Basic” Processes Can Lead to More Effective Medical Treatments

This schematic representation of a lipid droplet illustrates their complexity and overall structure. Courtesy of the Yale School of Medicine.

Gaining understanding of “basic” processes can often enable surprising discoveries and developments for disease treatment. According to new research under Yale’s Cell Biology Department, such is the case with the process of how cells store fat.

Yale Associate Professor Tobias Walther explained, “it’s a question of how you look at it […] we were interested in the mechanisms that a cell uses to store fat.” For Professor Walther, the principle of examining unresolved, forgotten scientific mysteries that are perceived to be well understood is what drives research. Walther’s work focuses on the mechanisms of plasma membrane organization and on the biology of cellular energy storage. In collaboration with Dr. Robert Farese of the University of California, San Francisco, Walther recently discovered that two distinct types of lipid droplets exist in the body, rather than just one as was previously believed.

This picture shows expanding lipid droplets in a cell along with the enzymes that trigger the expansion. Courtesy of the Yale School of Medicine.

The two types of droplets possess different properties. The first is small and does not grow, whereas the second expands due to the presence of what are known as triacylglycerol enzymes on its surface. Excess metabolic energy leads to the production of triacylglycerol, a compound that incorporates into the lipid droplets, which in turn are stored within adipose tissue in specialized fat cells. The extra energy results in rapid expansion of the second type of lipid droplet, causing a fattening of our bodies. Negative health consequences such as obesity and diabetes can result because fat cells struggle to store the excess energy. As Professor Walther explained, “it is not the presence of fat, but rather the cell’s inability to process excess energy that leads to health problems.” These findings have led to the development of drugs against the enzymes that allow for the synthesis of different lipids, currently in phase three clinical trials.

However, the discovery of these two types of lipid droplets and the synthesis of novel drugs is just the beginning of research on this topic. Professor Walther already has several future projects in mind. Among them is the biophysical analysis of the surface of the two different lipid droplets. Walther aims to discover how proteins are embedded in the lipid membranes and what structural differences are present between these lipid droplets and other lipids in the body. The biophysical analysis will allow for a better understanding of the overall structure and composition of the lipids. Furthermore, Walther seeks to analyze their physiological impact, which includes determining the fate of different lipid droplets and examining their functions. This research can lead to treatments for several diseases by focusing on different types of lipids and seeing how they function in the body.

These images display the structure of lipid droplets through fluorescence microscopy (left), electron microscopy (middle), and schematic representation (right). Courtesy of the Yale School of Medicine.

Until now, these details went unexamined. As Professor Walther’s work demonstrates, research in seemingly well-understood processes from a different angle can lead to groundbreaking discoveries with great implications.