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A nutrient responsive lipase mediates gut-brain communication to regulate insulin secretion in Drosophila
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A nutrient responsive lipase mediates gut-brain communication to regulate insulin secretion in Drosophila
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Journal Article
A nutrient responsive lipase mediates gut-brain communication to regulate insulin secretion in Drosophila
2024
Overview
Pancreatic β cells secrete insulin in response to glucose elevation to maintain glucose homeostasis. A complex network of inter-organ communication operates to modulate insulin secretion and regulate glucose levels after a meal. Lipids obtained from diet or generated intracellularly are known to amplify glucose-stimulated insulin secretion, however, the underlying mechanisms are not completely understood. Here, we show that a
Drosophila
secretory lipase, Vaha (CG8093), is synthesized in the midgut and moves to the brain where it concentrates in the insulin-producing cells in a process requiring Lipid Transfer Particle, a lipoprotein originating in the fat body. In response to dietary fat, Vaha stimulates insulin-like peptide release (ILP), and Vaha deficiency results in reduced circulatory ILP and diabetic features including hyperglycemia and hyperlipidemia. Our findings suggest Vaha functions as a diacylglycerol lipase physiologically, by being a molecular link between dietary fat and lipid amplified insulin secretion in a gut-brain axis.
Amplification of glucose stimulated insulin secretion by lipids is not fully understood due to complex inter organ communication in glycemic regulation. Here the authors show Vaha, a Drosophila lipase synthesized in the gut, concentrates in insulin producing cells in the brain to regulate insulin like peptide release.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/19
/ 64
/ 64/24
/ 82/51
/ 82/58
/ Animals
/ Brain
/ Drosophila Proteins - genetics
/ Drosophila Proteins - metabolism
/ Fat body
/ Glucose
/ Humanities and Social Sciences
/ Insects
/ Insulin
/ Insulin-Secreting Cells - metabolism
/ Lipase
/ Lipids
/ Lipoprotein Lipase - genetics
/ Lipoprotein Lipase - metabolism
/ Male
/ Midgut
/ Peptides
/ Science
