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

Abstract

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.

• Authors: Olga Kubrak, Takashi Koyama, Nadja Ahrentløv, Line Jensen, Alina Malita, Muhammad T Naseem, Mette Lassen, Stanislav Nagy, Michael J Texada, Kenneth V Halberg, Kim Rewitz
• Journal: Nature communications (Nat Commun) Vol. 13 Issue 1 Pg. 692 (02 04 2022) ISSN: 2041-1723 [Electronic] England
• PMID: 35121731 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• AstC protein, Drosophila
• AstC-R2 protein, Drosophila
• Drosophila Proteins
• Gastrointestinal Hormones
• Insect Hormones
• Oligopeptides
• Receptors, G-Protein-Coupled
• adipokinetic hormone
• Somatostatin
• Pyrrolidonecarboxylic Acid

Topics

• Animals
• Animals, Genetically Modified
• Drosophila Proteins (genetics, metabolism)
• Drosophila melanogaster (genetics, metabolism)
• Eating (genetics, physiology)
• Energy Metabolism (genetics, physiology)
• Enteroendocrine Cells (metabolism)
• Gastrointestinal Hormones (genetics, metabolism)
• Gene Knockout Techniques
• Homeostasis
• Humans
• Hypoglycemia (genetics, metabolism)
• Insect Hormones (genetics, metabolism)
• Nutrients (metabolism)
• Oligopeptides (genetics, metabolism)
• Pyrrolidonecarboxylic Acid (analogs & derivatives, metabolism)
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Signal Transduction (genetics)
• Somatostatin (genetics, metabolism)
• Survival Analysis