Biology of Lipid Storage

he supply and demand for metabolic energy in cells fluctuates. Therefore, organisms have evolved mechanisms to store metabolic energy. The most efficient and by far the most common way cells store energy is in the form of fat, particularly triacylglycerols (TGs). Although energy storage is inherently beneficial, overeating in today’s society has led to a global obesity and type 2 diabetes epidemic due in part, to the efficiency of these storage mechanisms.

In our laboratory, we study how metabolic energy is stored and how this process contributes to obesity and metabolic disease. In cells, TGs and other neutral lipids are synthesized in the ER and packaged into lipid droplets (LDs), compact cytosolic organelles that also store precursors for membrane and hormone synthesis. When energy is in short supply, lipids are mobilized from LDs. Lipid droplets therefore grow and shrink in cells to maintain lipid levels and meet metabolic demands.

Despite being discovered more than a century ago, many basic questions about LDs remain unanswered. How are LD formed? What controls their shrinkage and expansion? Our laboratory studies these fundamental questions using a wide range of cutting-edge interdisciplinary approaches, including biophysical, biochemical, and cell biological methods.

We also investigate the physiological importance of these lipid storage mechanisms in mouse models of obesity and metabolic disease. For instance, we are determining the physiological roles of different TG synthesis pathways in the lipid storage and secretion in mammalian tissues and the consequences that result when the storage capacity of these lipids is exceeded.

Read more:
Kory, N. et al. (2015) Protein crowding is a determinant of lipid droplet protein composition. Dev. Cell 34(3): 351-363.
Wilfling, F. et al. (2013) Triacylglycerol synthesis enzymes move from endoplasmic reticulum to lipid droplets to mediate lipid droplet growth. Dev. Cell 24(4): 384-399.
Krahmer, N. et al. (2011) Phosphatidylcholine Synthesis for Lipid Droplet Expansion: Targeted Activation of CTP:Phosphocholine Cytidylyltransferase, the Rate-Limiting Enzyme. Cell Metab. 14(4): 504-515.
Guo, Y. et al. (2008) Functional genomic screen reveals genes involved in lipid droplet formation and utilization. Nature 453(7195): 657-661.

Proteins compete for binding at the lipid droplet surface by a macromolecular crowding mechanism. Representative Drosophila S2 cells are shown. Note, image is pseudocolored for illustration purposes. Adapted from Kory, N. et al. (2015) Developmental Cell.