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Animal Models

Synphilin-1 alters metabolic homeostasis in a novel Drosophila obesity model

International Journal of Obesity volume 36, pages 1529–1536 (2012)Cite this article

Subjects

A Corrigendum to this article was published on 11 December 2012

Abstract

Aims:

The pathogenesis of obesity remains incompletely understood. Drosophila have conserved neuroendocrine and digestion systems with human and become an excellent system for studying energy homeostasis. Here, we reported a novel obesity Drosophila model, in which expression of human protein, synphilin-1 (SP1), in neurons fosters positive energy balance.

Subjects and methods:

To further understand the actions of SP1 in energy balance control, the upstream activation sequence UAS/GAL4 system was used to generate human SP1 transgenic Drosophila. We characterized a human SP1 transgenic Drosophila by assessing SP1 expression, fat lipid deposition, food intake and fly locomotor activity to determine the major behavioral changes and their consequences in the development of the obesity-like phenotype.

Results:

Overexpression of SP1 in neurons, but not peripheral cells, increased the body weight of flies compared with that of non-transgenic controls. SP1 increased food intake but did not affect locomotor activity. SP1 increased the levels of triacylglycerol, and the size of fat body cells and lipid droplets, indicating that SP1 increased lipid-fat disposition. Survival studies showed that SP1 transgenic flies were more resistant to food deprivation. SP1 regulated lipin gene expression that may participate in SP1-induced fat deposition and starvation resistance.

Conclusion:

These studies demonstrate that SP1 expression affects energy homeostasis in ways that enhance positive energy balance and provide a useful obesity model for future pathogenesis and therapeutic studies.

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Acknowledgements

We thank Dr Craig Montell for helpful discussion. We also thank Drs Bader Al-Anzi and Dr Youngseok Lee for kindly providing us the GAL4 driver flies. This work was supported by the National Institutes of Health, Grants: DK083410 to WWS, and the Paul R McHugh Chair for Motivated Behavior to THM.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA

    J Liu, T Li, D Yang, R Ma & W W Smith

  2. Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    T H Moran

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  1. J Liu
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Correspondence to W W Smith.

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Liu, J., Li, T., Yang, D. et al. Synphilin-1 alters metabolic homeostasis in a novel Drosophila obesity model. Int J Obes 36, 1529–1536 (2012). https://doi.org/10.1038/ijo.2012.111

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