Maintaining systemic energy homeostasis is crucial for the physiology of all living organisms. This process involves a tight control of cellular and organismal metabolic functions, which are required to coordinate energy intake and energy expenditure. Disruption of this balance can lead to major human pathologies, such as diabetes, obesity and lipodystrophy.
A central regulator of systemic metabolism is the intestine. The intestinal epithelium is responsible for nutrient absorption, as well as being a key-endocrine and immune tissue. Due to its endocrine function, the intestine orchestrates the communication between multiple organs, which is required to maintain organismal fitness in response to changing environmental and nutrient demands.
Functional studies on inter-organ communication are often challenging in mammalian systems, due to their complex physiology. A simpler, yet relevant organism like Drosophila melanogaster has proven to be an invaluable alternative model system to study complex physiological processes.
In this thesis we used Drosophila melanogaster as a paradigm to study how the intestine communicates with other tissues through its endocrine function to regulate systemic metabolic homeostasis.
We found that systemic secretion of the intestinal enteroendocrine derived hormone Bursicon is regulated by nutrients and maintains metabolic homeostasis via its neuronal receptor LGR2. Impairment of Bursicon/ neuronal LGR2 signalling resulted in extensive loss of stored energy resources, especially lipids.
Our data provides new insights into intestinal endocrine regulation of metabolic homeostasis. Our work identified a novel gut/brain axis controlling key metabolic tissues. Using Drosophila to identify gut-dependent hormonal metabolic networks will help to gain a deeper knowledge of how organs communicate with each other to maintain systemic metabolic homeostasis, which could impact the identification of therapeutic targets for metabolic disorders in humans
