A nutrient responsive lipase mediates gut-brain communication to regulate insulin secretion in Drosophila
Alka Singh, Kandahalli Venkataranganayaka Abhilasha, Kathya R. Acharya, Haibo Liu, Niraj K. Nirala, Velayoudame Parthibane, Kunduri Govind, Thiruvaimozhi Abimannan, Jacob Tantalla, Lihua Julie Zhu, Jairaj Acharya, Usha Acharya
Abstract
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.