Open Access Highly Accessed Research article

Loss of IP3 receptor function in neuropeptide secreting neurons leads to obesity in adult Drosophila

Manivannan Subramanian12, Siddharth Jayakumar13, Shlesha Richhariya1 and Gaiti Hasan1*

Author Affiliations

1 National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India

2 Mysore University, Mysore 570006, India

3 Manipal University, Manipal 576104, India

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BMC Neuroscience 2013, 14:157  doi:10.1186/1471-2202-14-157

Published: 18 December 2013

Abstract

Background

Intracellular calcium signaling regulates a variety of cellular and physiological processes. The inositol 1,4,5 trisphosphate receptor (IP3R) is a ligand gated calcium channel present on the membranes of endoplasmic reticular stores. In previous work we have shown that Drosophila mutants for the IP3R (itprku) become unnaturally obese as adults with excessive storage of lipids on a normal diet. While the phenotype manifests in cells of the fat body, genetic studies suggest dysregulation of a neurohormonal axis.

Results

We show that knockdown of the IP3R, either in all neurons or in peptidergic neurons alone, mimics known itpr mutant phenotypes. The peptidergic neuron domain includes, but is not restricted to, the medial neurosecretory cells as well as the stomatogastric nervous system. Conversely, expression of an itpr+ cDNA in the same set of peptidergic neurons rescues metabolic defects of itprku mutants. Transcript levels of a gene encoding a gastric lipase CG5932 (magro), which is known to regulate triacylglyceride storage, can be regulated by itpr knockdown and over-expression in peptidergic neurons. Thus, the focus of observed itpr mutant phenotypes of starvation resistance, increased body weight, elevated lipid storage and hyperphagia derive primarily from peptidergic neurons.

Conclusions

The present study shows that itpr function in peptidergic neurons is not only necessary but also sufficient for maintaining normal lipid metabolism in Drosophila. Our results suggest that intracellular calcium signaling in peptidergic neurons affects lipid metabolism by both cell autonomous and non-autonomous mechanisms.

Keywords:
Calcium; Lipid homeostasis; Hyperphagia; Magro