The gut hormone Allatostatin C/Somatostatin regulates food intake and metabolic homeostasis under nutrient stress

• Published in: Nature communications Vol. 13; no. 1; p. 692
• Main Authors: Kubrak, Olga, Koyama, Takashi, Ahrentløv, Nadja, Jensen, Line, Malita, Alina, Naseem, Muhammad T., Lassen, Mette, Nagy, Stanislav, Texada, Michael J., Halberg, Kenneth V., Rewitz, Kim
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.02.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/51; 13/89; 14/19; 38/77; 38/90; 45/41; 631/443/319/1488; 631/443/319/1557; 64/24; 692/163/2743/137; 82/51; 96; Adaptation; Animals; Animals, Genetically Modified; Digestive system; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Eating - genetics; Eating - physiology; Energy balance; Energy Metabolism - genetics; Energy Metabolism - physiology; Enteroendocrine Cells - metabolism; Food; Food intake; Fruit flies; Gastrointestinal Hormones - genetics; Gastrointestinal Hormones - metabolism; Gastrointestinal tract; Gene Knockout Techniques; Glucagon; Homeostasis; Homology; Hormones; Humanities and Social Sciences; Humans; Hypoglycemia; Hypoglycemia - genetics; Hypoglycemia - metabolism; Insect Hormones - genetics; Insect Hormones - metabolism; Insects; Intestine; Lipids; Metabolic disorders; Metabolism; multidisciplinary; Nutrients; Nutrients - metabolism; Nutritive value; Oligopeptides - genetics; Oligopeptides - metabolism; Organs; Pyrrolidonecarboxylic Acid - analogs & derivatives; Pyrrolidonecarboxylic Acid - metabolism; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Science; Science (multidisciplinary); Signal Transduction - genetics; Somatostatin; Somatostatin - genetics; Somatostatin - metabolism; Survival Analysis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28268-x

The intestine is a central regulator of metabolic homeostasis. Dietary inputs are absorbed through the gut, which senses their nutritional value and relays hormonal information to other organs to coordinate systemic energy balance. However, the gut-derived hormones affecting metabolic and behavioral responses are poorly defined. Here we show that the endocrine cells of the Drosophila gut sense nutrient stress through a mechanism that involves the TOR pathway and in response secrete the peptide hormone allatostatin C, a Drosophila somatostatin homolog. Gut-derived allatostatin C induces secretion of glucagon-like adipokinetic hormone to coordinate food intake and energy mobilization. Loss of gut Allatostatin C or its receptor in the adipokinetic-hormone-producing cells impairs lipid and sugar mobilization during fasting, leading to hypoglycemia. Our findings illustrate a nutrient-responsive endocrine mechanism that maintains energy homeostasis under nutrient-stress conditions, a function that is essential to health and whose failure can lead to metabolic disorders. Intestinal nutrient-sensing is important in metabolic control. Here the authors show that the gut-derived hormone Allatostatin C, a somatostatin homolog in fruit flies, links enteric nutrient sensing to behavioral and metabolic adaptations that maintain energetic homeostasis in Drosophila melanogaster.