Gould lab

Physiology and Metabolism Laboratory

: Lipid metabolism during growth and stress

Lipids play numerous different roles in health and disease. Some lipids function as metabolic fuels for energy homeostasis, others act as components of cell membranes and some serve as signalling molecules. Neutral lipids relevant for energy homeostasis, such as triglycerides and cholestryl esters, are stored inside cells within lipid droplets.

These lipid droplets are important organelles consisting of a neutral lipid core surrounded by a phospholipid monolayer containing lipases and many other proteins regulating fat metabolism. Current work in the lab explores the physiological roles of lipid droplets in a number of different biological contexts and disease models.

Research in the lab has identified an unexpected role for lipid droplets as an antioxidant organelle. This research began with the observation that lipid droplets in the developing Drosophila CNS are induced by reactive oxygen species (ROS) generated by environmental exposure to hypoxia and other pro-oxidants.

Lipid droplets form in the glia of the stem cell (neuroblast) niche during oxidative stress and function to limit ROS levels and to inhibit the peroxidation of polyunsaturated fatty acids (PUFAs). These droplets protect glia and also neuroblasts from peroxidation chain reactions that can damage many types of macromolecules. The underlying antioxidant mechanism involves diverting PUFAs, including diet-derived linoleic acid, away from membranes to the core of lipid droplets, where they are less vulnerable to peroxidation. We are now testing whether the antioxidant role for lipid droplets is relevant in other Drosophila and mammalian contexts.

Oenocytes are mysterious insect cells that were first observed in the 1850s but whose functions remained elusive until the 2000s. We discovered that Drosophila oenocytes express genes indicative of highly specialized role(s) in fatty acid metabolism and that they are essential for the growth of the larva. We found that they accumulate lipid droplets during starvation by a mechanism that requires fat mobilization from the major insect adipose store, the fat body. Hence, at least in terms of nutritional regulation, there are interesting similarities between the mammalian adipose-liver and the insect fat body-oenocyte axes.

The physiological functions of oenocytes appear to be linked to their ability to synthesize very long chain fatty acids (VLCFAs). Other labs have shown that, in larvae, oenocyte VLCFAs are involved in tracheal waterproofing and that, in adults, they are metabolized into pheromones. Our current work in this area focuses on identifying the mechanisms by which dietary nutrients regulate oenocytes.