Delivery of circulating lipoproteins to specific neurons in the Drosophila brain regulates systemic insulin signaling.

Marko Brankatschk,Sebastian Dunst,Suzanne Eaton,Linda Nemetschke

doi:10.7554/elife.02862

Marko Brankatschk, Sebastian Dunst + Show 2 more

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https://doi.org/10.7554/elife.02862

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Abstract

The Insulin signaling pathway couples growth, development and lifespan to nutritional conditions. Here, we demonstrate a function for the Drosophila lipoprotein LTP in conveying information about dietary lipid composition to the brain to regulate Insulin signaling. When yeast lipids are present in the diet, free calcium levels rise in Blood Brain Barrier glial cells. This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin. LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation. This increases systemic Insulin signaling and the rate of larval development on yeast-containing food compared with a plant-based food of similar nutritional content.

Highlights

Nutrient sensing by the central nervous system is emerging as an important regulator of systemic metabolism in both vertebrates and invertebrates (Lam et al, 2005; Levin et al, 2011; Rajan and Perrimon, 2012; Bjordal et al, 2014; Linneweber et al, 2014)
Drosophila do not have a single pancreas-like organ, they do produce eight distinct Drosophila Insulin/IGF-like peptides (Dilps) that are expressed in different tissues (Riedel et al, 2011; Colombani et al, 2012; Garelli et al, 2012)
LTP particles secreted by the fat body cross the Blood Brain Barrier and become enriched on specific neurons

Summary

Introduction

Nutrient sensing by the central nervous system is emerging as an important regulator of systemic metabolism in both vertebrates and invertebrates (Lam et al, 2005; Levin et al, 2011; Rajan and Perrimon, 2012; Bjordal et al, 2014; Linneweber et al, 2014). Insulin and Insulin-like growth factors are conserved systemic signals that regulate growth and metabolism in response to nutrition. A set of three Dilps (Dilp2,3,5), released into circulation by Dilp-producing cells (IPCs) in the brain, have important functions in regulating nutrition-dependent growth and sugar metabolism; ablation of IPCs in the CNS causes Diabetes-like phenotypes, slows growth and development, and produces small, long-lived adult flies (Rulifson et al, 2002; Broughton et al, 2005; Partridge et al, 2011). Sugars act on IPCs directly to promote Dilp release (Haselton and Fridell, 2010), but other nutrients are sensed indirectly through signals from the fat body—an organ analogous to vertebrate liver/adipose tissue (Colombani et al, 2003; Geminard et al, 2009; Rajan and Perrimon, 2012)

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