Metabolic dysregulation and resistance to high-fat diet-induced weight gain in mice overexpressing human wild-type α-synuclein
Abstract Unintentional weight loss is common among patients with Parkinson’s disease (PD) and is associated with poor quality of life and accelerated disease progression. To explore how early α-synuclein pathology contributes to metabolic dysregulation leading to weight loss in PD, transgenic mice o...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-04-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-025-00961-w |
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| Summary: | Abstract Unintentional weight loss is common among patients with Parkinson’s disease (PD) and is associated with poor quality of life and accelerated disease progression. To explore how early α-synuclein pathology contributes to metabolic dysregulation leading to weight loss in PD, transgenic mice overexpressing human wild-type α-synuclein (α-Syn) and controls were fed a high-fat diet (HFD) chow for 4 months. Compared with controls on HFD, α-Syn mice on HFD exhibited a dramatically leaner phenotype, improved glucose tolerance, a major decrease in fat mass, an increase in energy expenditure, a decrease in insulin signaling in the olfactory bulb, aggravated olfactory and motor dysfunctions, and an increase in mortality. Our results show that high-fat diet in α-Syn mice provides a sensitive tool for assessing the underlying mechanism of metabolic dysfunction and its impact on weight loss and disease progression in PD. Moreover, a role is proposed for olfactory dysfunction in PD-related unintentional weight loss. |
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| ISSN: | 2373-8057 |