An adipocyte protein promotes the growth of lipid droplets (LDs) by facilitating lipid transfer from smaller to larger droplets, Gong et al. report.

Consisting of a neutral lipid core surrounded by a monolayer of phospholipids and associated proteins, LDs serve as the cell's fat storage depots, particularly in adipocytes where they grow to extra large sizes. How LDs grow is unknown, but adipocytes lacking the LD-associated protein Fsp27 have many small droplets instead of a single large one.

Gong et al. found that Fsp27 concentrated at the contacts between LDs and that this localization depended on the protein's C-terminal domain. Photobleaching experiments revealed that LDs in contact with each other traded neutral lipids but that this exchange was abolished in adipocytes lacking Fsp27. Moreover, the researchers identified three lysine residues—which may form part of an amphipathic helix in Fsp27's C terminus—that were required for lipid exchange and LD growth.

Although LDs exchanged lipids bidirectionally, net lipid transfer occurred from the smaller to the larger droplet of an LD pair, leading to shrinkage of the smaller droplet and growth of the larger one. This directional transfer is probably driven by the higher internal pressure within smaller droplets, which would force lipids into the larger LD.

How Fsp27 facilitates this transfer remains unclear, but senior author Peng Li thinks that the protein may help to connect LDs and form a pore to allow lipid movement. The next question, she says, is to identify additional proteins that work with Fsp27 to boost LD growth.

et al
J. Cell Biol.