The Drosophila model to interrogate triacylglycerol biology

The deposition of storage fat in the form of triacylglycerol (TAG) is an evolutionarily conserved strategy to cope with fluctuations in energy availability and metabolic stress. Organismal TAG storage in specialized adipose tissues provides animals a metabolic reserve that sustains survival during development and starvation. On the other hand, excessive accumulation of adipose TAG, defined as obesity, is associated with an increasing prevalence of human metabolic diseases. During the past decade, the fruit fly Drosophila melanogaster, traditionally used in genetics and developmental biology, has been established as a versatile model system to study TAG metabolism and the etiology of lipid-associated metabolic diseases. Similar to humans, Drosophila TAG homeostasis relies on the interplay of organ systems specialized in lipid uptake, synthesis, and processing, which are integrated by an endocrine network of hormones and messenger molecules. Enzymatic formation of TAG from sugar or dietary lipid, its storage in lipid droplets, and its mobilization by lipolysis occur via mechanisms largely conserved between Drosophila and humans. Notably, dysfunctional Drosophila TAG homeostasis occurs in the context of aging, overnutrition, or defective gene function, and entails tissue-specific and organismal pathologies that resemble human disease. In this review, we summarize the physiology and biochemistry of TAG in Drosophila and outline the potential of this organism as a model system to understand the genetic and dietary basis of TAG storage and TAG-related metabolic disorders.