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A novel obesity model: synphilin-1-induced hyperphagia and obesity in mice

International Journal of Obesity volume 36, pages 1215–1221 (2012)Cite this article

Subjects

Abstract

Aims:

The pathogenesis of obesity remains incompletely understood and the exploration of the role of novel proteins in obesity may provide important insights into its causes and treatments. Here, we report a previously unidentified role for synphilin-1 in the control of food intake and body weight. Synphilin-1, a cytoplasmic protein, was initially identified as an interaction partner of alpha-synuclein, and has implications in Parkinson's disease pathogenesis related to protein aggregation.

Subjects and methods:

To study the in vivo role of synphilin-1, we characterized a human synphilin-1 transgenic mouse (SP1) by assessing synphilin-1 expression, plasma parameters, food intake and spontaneous activity to determine the major behavioral changes and their consequences in the development of the obesity phenotype.

Results:

Expression of human synphilin-1 in brain neurons in SP1 mice resulted in increased food intake, body weight and body fat. SP1 mice also displayed hyperinsulinemia, hyperleptinemia and impaired glucose tolerance. Pair-feeding SP1 mice to amounts consumed by non-transgenic mice prevented the increased body weight, adiposity, hyperinsulinemia and hyperleptinemia demonstrating that these were all the consequences of increased food intake. Transgenic expression of synphilin-1 was enriched in hypothalamic nuclei involved in feeding control, and fasting-induced elevated endogenous synphilin-1 levels at these sites, suggesting that synphilin-1 is an important player in the hypothalamic energy balance regulatory system.

Conclusion:

These studies identify a novel function of synphilin-1 in controlling food intake and body weight, and may provide a unique obesity model for future studies of obesity pathogenesis and therapeutics.

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Acknowledgements

We thank Yi Yu, Jayson Hyun, Megan Smith and Guangjing Zhu for technical support. We thank Dr T Dawson for read the manuscript. This work was supported by National Institutes of Health, Grants: DK083410 to WWS, NS38377 to CAS, DK19302 and DK068054, and the Paul R. McHugh Chair for Motivated Behavior to THM.

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Author notes

  1. X Li

    Present address: 4Current address: Xi’an Medical University, Xi’an, China.,

Authors and Affiliations

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

    X Li, Z Liu & W W Smith

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

    K L K Tamashiro, N T Bello, X Wang, S Aja, S Bi, E E Ladenheim, C A Ross & T H Moran

  3. Departments of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    C A Ross

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  1. X Li
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Correspondence to W W Smith.

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Li, X., Tamashiro, K., Liu, Z. et al. A novel obesity model: synphilin-1-induced hyperphagia and obesity in mice. Int J Obes 36, 1215–1221 (2012). https://doi.org/10.1038/ijo.2011.235

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