Discovering signaling mechanisms governing metabolism and metabolic diseases with Drosophila

• Published in: Cell metabolism 2021-07, Vol.33 (7), p.1279-1292
• Main Authors: Kim, Seung K., Tsao, Deborah D., Suh, Greg S.B., Miguel-Aliaga, Irene
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; diabetes; disease; Disease Models, Animal; Drosophila melanogaster; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; endocrinology; Energy Metabolism - genetics; gastrointestinal tract; genetics; hormones; Humans; intestine; Metabolic Diseases - etiology; Metabolic Diseases - genetics; Metabolic Diseases - metabolism; Metabolic Diseases - pathology; Models, Biological; neuron; physiology; sexual dimorphism; Signal Transduction - physiology
• ISSN: 1550-4131; 1932-7420; 1932-7420
• DOI: 10.1016/j.cmet.2021.05.018

There has been rapid growth in the use of Drosophila and other invertebrate systems to dissect mechanisms governing metabolism. New assays and approaches to physiology have aligned with superlative genetic tools in fruit flies to provide a powerful platform for posing new questions, or dissecting classical problems in metabolism and disease genetics. In multiple examples, these discoveries exploit experimental advantages as-yet unavailable in mammalian systems. Here, we illustrate how fly studies have addressed long-standing questions in three broad areas—inter-organ signaling through hormonal or neural mechanisms governing metabolism, intestinal interoception and feeding, and the cellular and signaling basis of sexually dimorphic metabolism and physiology—and how these findings relate to human (patho)physiology. The imaginative application of integrative physiology and related approaches in flies to questions in metabolism is expanding, and will be an engine of discovery, revealing paradigmatic features of metabolism underlying human diseases and physiological equipoise in health. Kim et al. review growth of powerful systems in fruit flies to discover conserved cellular and signaling mechanisms regulating metabolism and metabolic disease pathogenesis. They focus on hormonal and neural signaling mechanisms that govern metabolism, interoception and feeding, and sexually dimorphic physiology, and illustrate mechanistic links to cognate human states.