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

Liu, J; Li, T; Yang, D; Ma, R; Moran, T H; Smith, W W
December 2012
International Journal of Obesity;Dec2012, Vol. 36 Issue 12, p1529
Academic Journal
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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