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

X. Li, K. L.K. Tamashiro, Z. Liu, N. T. Bello, X. Wang, S. Aja, S. Bi, E. E. Ladenheim, C. A. Ross, T. H. Moran, W. W. Smith

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1215-1221
Number of pages7
JournalInternational Journal of Obesity
Volume36
Issue number9
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Keywords

  • ARC
  • PVN
  • Synphilin-1
  • body weight
  • fat
  • food intake

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    Li, X., Tamashiro, K. L. K., Liu, Z., Bello, N. T., Wang, X., Aja, S., Bi, S., Ladenheim, E. E., Ross, C. A., Moran, T. H., & Smith, W. W. (2012). A novel obesity model: Synphilin-1-induced hyperphagia and obesity in mice. International Journal of Obesity, 36(9), 1215-1221. https://doi.org/10.1038/ijo.2011.235