Drosophila as a Genetic Model System to Study Organismal Energy Metabolism

Abstract

Metabolism is the essential process by which an organism converts nutrients into energy to fuel growth, development, and repair. Metabolism at the level of a multicellular, multi-organ animal is inherently more complex than metabolism at the single-cell level. Indeed, each organ also must maintain its own homeostasis to function. At all three scales, homeostasis is a defining feature: as energy sources and energetic demands wax and wane, the system must be robust. While disruption of organismal energy homeostasis can be manifested in different ways in humans, obesity (defined as excess body fat) is an increasingly common outcome of metabolic imbalance. Here we will discuss the genetic basis of metabolic dysfunction that underlies obesity. We focus on what we are learning from Drosophila melanogaster as a model organism to explore and dissect genetic causes of metabolic dysfunction in the context of a whole organism.

Keywords: Drosophila; metabolism; obesity.

Figure 1

Genetic screens in Drosophila identify candidate human obesity genes. The three genetic screens for which results are detailed in Table 1 are schematized here. Two screens in adults and one screen in larvae generated lists of candidate genes regulating fat storage. Some known and predicted functional categories corresponding to these genes are illustrated in the center. The human figure below illustrates how information about the Drosophila genes can be used to inform interpretation of human obesity GWAS studies and how human obesity GWAS studies can be used to guide Drosophila genetic screens.