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, Govind Kunduri, Thiruvaimozhi Abimannan, Jacob Tantalla, Lihua Julie Zhu, Jairaj K. Acharya () and Usha R. Acharya ()
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Alka Singh: UMass Chan Medical School
Kandahalli Venkataranganayaka Abhilasha: National Cancer Institute
Kathya R. Acharya: UMass Chan Medical School
Haibo Liu: UMass Chan Medical School
Niraj K. Nirala: UMass Chan Medical School
Velayoudame Parthibane: National Cancer Institute
Govind Kunduri: National Cancer Institute
Thiruvaimozhi Abimannan: National Cancer Institute
Jacob Tantalla: National Cancer Institute
Lihua Julie Zhu: UMass Chan Medical School
Jairaj K. Acharya: National Cancer Institute
Usha R. Acharya: National Cancer Institute

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48851-8

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