Coordination between Drosophila Arc1 and a specific population of brain neurons regulates organismal fat

Abstract

The brain plays a critical yet incompletely understood role in regulating organismal fat. We performed a neuronal silencing screen in Drosophila larvae to identify brain regions required to maintain proper levels of organismal fat. When used to modulate synaptic activity in specific brain regions, the enhancer-trap driver line E347 elevated fat upon neuronal silencing, and decreased fat upon neuronal activation. Unbiased sequencing revealed that Arc1 mRNA levels increase upon E347 activation. We had previously identified Arc1 mutations in a high-fat screen. Here we reveal metabolic changes in Arc1 mutants consistent with a high-fat phenotype and an overall shift toward energy storage. We find that Arc1-expressing cells neighbor E347 neurons, and manipulating E347 synaptic activity alters Arc1 expression patterns. Elevating Arc1 expression in these cells decreased fat, a phenocopy of E347 activation. Finally, loss of Arc1 prevented the lean phenotype caused by E347 activation, suggesting that Arc1 activity is required for E347 control of body fat. Importantly, neither E347 nor Arc1 manipulation altered energy-related behaviors. Our results support a model wherein E347 neurons induce Arc1 in specific neighboring cells to prevent excess fat accumulation.

An autonomous metabolic role for Spen

“…Pre-wandering L3 larvae were collected and tracked for movement as previously described [ 87 ]. n = 4.…”

Drosophilaas a model to study obesity and metabolic disease

“…Collections of laboratory-generated and naturally occurring genetic variants isolated from all over the world make Drosophila an ideal model in which to test the effects of genes on obesity (Reed et al, 2010;Reis et al, 2010, among others). Genetic screens using these and other resources have identified genes that confer obesity in Drosophila via TAG quantification or buoyancy screening (Baumbach et al, 2014a;Lee et al, 2014;Mosher et al, 2015;Reis et al, 2010). Microscopy-based genome-wide in vitro screens have identified genes that modulate cellular lipid storage in Drosophila tissue culture cells (Beller et al, 2008;Guo et al, 2008).…”

Structures of virus-like capsids formed by the Drosophila neuronal Arc proteins

“…At least two Arc homologues (dArc1 and dArc2) are found in the brachyceran fly lineage, which arose by genomic duplication of an ancestral dArc gene 4,5 . dArc1 is implicated in modulating synaptic plasticity at the neuro-muscular junction 5 and in controlling fat metabolism 6,7 . dArc2 has no assigned function.…”