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A novel obesity model: synphilin-1-induced hyperphagia and obesity in mice
1Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
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.
Insights
Synphilin-1, a novel protein, significantly increases food intake and body weight in mice. This discovery offers a new model for studying obesity and potential therapeutic targets.
Area of Science:
- Neuroscience
- Metabolic Research
- Molecular Biology
Background:
- The precise mechanisms driving obesity pathogenesis are not fully understood.
- Identifying novel proteins involved in appetite regulation is crucial for developing effective obesity treatments.
- Synphilin-1, a cytoplasmic protein, was previously linked to alpha-synuclein and Parkinson's disease.
Purpose of the Study:
- To investigate the role of synphilin-1 in regulating food intake and body weight.
- To characterize a novel synphilin-1 transgenic mouse model (SP1) for obesity research.
Main Methods:
- Generated and analyzed human synphilin-1 transgenic mice (SP1).
- Assessed synphilin-1 expression, plasma parameters, food intake, and spontaneous activity.
- Conducted pair-feeding studies to differentiate direct effects from consequences of overeating.
Main Results:
- SP1 mice exhibited increased food intake, body weight, adiposity, hyperinsulinemia, hyperleptinemia, and impaired glucose tolerance.
- These metabolic changes were directly attributed to increased food intake, as prevented by pair-feeding.
- Synphilin-1 expression was concentrated in hypothalamic feeding control centers, with elevated levels during fasting.
Conclusions:
- Synphilin-1 plays a novel and significant role in controlling food intake and body weight.
- The SP1 mouse model provides a valuable tool for future obesity research and therapeutic development.
- Synphilin-1 is implicated as a key regulator within the hypothalamic energy balance system.
