Diabetic larvae and obese flies-emerging studies of metabolism in Drosophila

Abstract

The past few years have seen a shift in the use of Drosophila, from studies of growth and development toward genetic characterization of carbohydrate, sterol, and lipid metabolism. This research, reviewed below, establishes a new foundation for using this simple genetic model system to define the basic regulatory mechanisms that underlie metabolic homeostasis and holds the promise of providing new insights into the causes and treatments of critical human disorders such as diabetes and obesity.

Figure 1

Schematic representation of signaling pathways that regulate Drosophila metabolism. Functional interactions described in the text are depicted for a fat body cell under both fed and starved conditions. Solid lines and arrows represent signaling interactions, while dotted lines and arrows represent regulatory effects that occur in the absence of that signaling pathway. In the fed condition (top), DILPs and nutrients signal through the insulin and TOR pathways, respectively, resulting in retention of FOXO in the cytoplasm and increased translation, driving growth. Sugars and fatty acids are stored as glycogen and TAG, while energy-producing metabolic pathways are down-regulated. In starved animals (bottom), insulin and TOR signaling is attenuated, directing FOXO nuclear translocation and reducing protein synthesis, restricting growth. Glycogen and TAG are mobilized by AKH and lipases such as Brummer, while energy producing metabolic pathways are up-regulated. See text for more details.