TY - JOUR
T1 - The gut hormone Allatostatin C/Somatostatin regulates food intake and metabolic homeostasis under nutrient stress
AU - Kubrak, Olga
AU - Koyama, Takashi
AU - Ahrentloev, Nadja
AU - Jensen, Line
AU - Malita, Alina
AU - Naseem, Muhammad Tayyib
AU - Lassen, Mette
AU - Nagy, Stanislav
AU - Texada, Michael
AU - Halberg, Kenneth
AU - Rewitz, Kim
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-022-28268-x
DO - 10.1038/s41467-022-28268-x
M3 - Journal article
C2 - 35121731
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 692
ER -