Real-Time Imaging of Lipid Metabolism in Larval Zebrafish

Abstract

Many fundamental questions remain regarding the cellular and molecular mechanisms of lipid metabolism. One major impediment to answering important questions in the field has been the lack of a tractable and sufficiently complex model system. Until recently, most studies of lipid metabolism have been performed in vitro or in the mouse, yet each approach possesses certain limitations. The zebrafish (Danio rerio) offers an excellent model system with which to study lipid metabolism in vivo due to its small size, genetic tractability and optical clarity. We have exploited the unique advantages of the zebrafish to visualize digestive processes in vivo by using a number of fluorescent tools, including fluorescent reporters of lipase and protease activity, fluorescent lipid analogs, and fluorescent microspheres. Using these tools with the zebrafish model system enables one to generate visible readouts of digestive physiology and organ function in real time. Additionally, the zebrafish system is amenable to highthroughput approaches to identify small molecules that influence lipid metabolism and new pharmaceuticals for the treatment of human lipid disorders. In this chapter we present recent advances in visualizing lipid metabolism in live larval zebrafish with a focus on fatty acid metabolism.