Yale Graduate School of Arts and Sciences

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Studying Obesity on a Cellular Level

Florian Wilfling (Cell Biology) studies how fat is metabolized – a longstanding scientific mystery that is closely tied to a well documented medical problem. Fat droplets have the ability to expand dramatically in order to absorb fatty acids when the body takes in more food than it needs for energy. The ultimate result, if this process goes unchecked, is obesity.

“Everybody has seen the phenomenon of oil drops on top of a bowl of soup,” Florian says. “This occurs because of a 'phase separation' between the water and the oil." As cells consist of water, they must overcome this problem of phase separation in order to store fat. To this end, Flavian explains, "cells have developed an organelle that allows the storage of fat in an aqueous environment in a regulated way.”

Organelles are specialized subunits within a cell that carry out a specific function. The organelles Florian refers to are called lipid droplets. Unlike most organelles, lipid droplets are comprised of a phospholipid monolayer. The outer surface of the lipid droplet faces the aqueous surface (and is thus called "hydrophilic") while the inner surface surrounds and encapsulates a core of fat (and is thus called "hydrophobic").

“The size and abundance of lipid droplets can vary according to the needs of the cell,” Florian says. “Lipid droplets can expand quickly over several orders of magnitude and quickly contract again. We were trying to understand how that happens.”

For this study, Florian participated on a team led by Tobias Walther, his dissertation adviser, and which included scientists from the Gladstone Institutes in San Francisco. Their experiments revealed that a phospholipid called phosphatidylcholine (PC) is required for cells to grow lipid droplets in a regulated manner. Without a steady supply of PC, which lowers the surface tension of a liquid, lipid droplet membranes lose strength, causing them to fuse just as separate oil drops fuse in water – or, as with Florian's example cited above, on the surface of soup. Additional PC is needed to coat the enlarging surface area during lipid droplet expansion, and that is provided by enzymes within the cell.

An enzyme called CCT inside the cell senses tension at the surface of the expanding fat droplets, triggering the production of more PC to enable the cell to expand and accommodate additional fatty acids without adverse consequences. The process is crucial for the fat cells to remain in harmony with their environment.

“We discovered how the cell can sense PC deficiency on expanding lipid droplets and react to that deficiency,” Florian says. The discovery was reported in the journal Cell Metabolism last fall.

Walther further explains, “Without this mechanism, fat droplets within cells where energy is stored undergo quick expansion and form one big clump” instead of remaining as individual droplets. “The cells must balance fluctuations in energy availability, and we are exploring other mechanisms that help maintain this dynamic storage capacity.”

This process on a cellular level is analgous to the all-too-common occurrence when an individaul consumes more food than he requires for energy. Lipid droplets fuse, fat begins to accumulate, and the cell mechanisms responsible for energy mobilization fail, increasing the likelihood of obesity and all its attendant health problems.

“Dozens of things go wrong at the same time when cells are overwhelmed by excess fat storage, and the million-dollar question is: Which of these factors cause the breakdown of cellular balance?” Walther asks.

Although this project is not part of Florian's dissertation, it fits right into his research. “I am fascinated by the fact that a single cell can do all different tasks, and Walther's lab is a very good one to study the way lipid droplets function,” he says. His primary research involves a study of the enzymes necessary to produce the fat, triacylglycerol.

Before coming to Yale, Florian earned his undergraduate degree from the Technical University of Munich.

Florian Wilfling