Model Organisms in Drug Discovery

8
Lipid Metabolism and
Signaling in Zebrafish
Shiu-Ying Ho, Steven A. Farber and Michael Pack
Although best known as a model organism used in developmental studies, the
zebrafish is also suited to physiological analysis. Zebrafish process dietary
lipids in a manner that closely resembles humans, and lipid metabolism can be
inhibited by drugs used to treat human lipid disorders. Zebrafish also utilize
prostanoid lipid signaling molecules, such as the prostaglandins and
thromboxanes, and their synthesis can be inhibited by commonly prescribed
non-steroidal antiinflammatory drugs. This chapter reviews studies devoted to
lipid metabolism in zebrafish and identifies screening strategies for the
identification of novel regulators of dietary lipid processing and prostanoid
synthesis.
8.1 Introduction
As components of cell membranes, mediators of cell signaling and an energy
source, lipids play an essential role in the physiology of all vertebrate cells.
Given such diverse roles, it is not surprising that lipids also are important
modulators of human disease. Perturbation of lipid metabolism is associated
with heritable and acquired disease syndromes that predispose affected
individuals to diabetes mellitus and atherosclerosis (Garg, 1998; Pajukanta
and Porkka, 1999; Joffe et al., 2001; McNeely et al., 2001). Lipid mediators
also regulate the activation of immune cells associated with these conditions
Model Organisms in Drug Discovery. Edited by Pamela M. Carroll and Kevin Fitzgerald
Copyright © 2003 John Wiley & Sons, Ltd. ISBN: 0-470-84893-6