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过表达人野生型α-突触核蛋白的小鼠的代谢失调及对高脂饮食诱导的体重增加的抵抗

Metabolic dysregulation and resistance to high-fat diet-induced weight gain in mice overexpressing human wild-type α-synuclein.

作者信息

Biju K C, Torres Hernandez Enrique, Stallings Alison Michelle, Felix-Ortiz Ada C, Hebbale Skanda K, Norton Luke, Mader Michael J, Clark Robert A

机构信息

South Texas Veterans Health Care System, San Antonio, TX, USA.

Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

出版信息

NPJ Parkinsons Dis. 2025 Apr 24;11(1):90. doi: 10.1038/s41531-025-00961-w.

DOI:10.1038/s41531-025-00961-w
PMID:40274795
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12022322/
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.

摘要

帕金森病（PD）患者中，非故意性体重减轻很常见，且与生活质量差和疾病进展加速相关。为探究早期α-突触核蛋白病理学如何导致代谢失调进而引发PD患者体重减轻，将过表达人类野生型α-突触核蛋白（α-Syn）的转基因小鼠和对照组小鼠喂食高脂饮食（HFD）4个月。与喂食HFD的对照组相比，喂食HFD的α-Syn小鼠表现出显著更瘦的表型、改善的葡萄糖耐量、脂肪量大幅减少、能量消耗增加、嗅球中胰岛素信号传导减少、嗅觉和运动功能障碍加重以及死亡率增加。我们的结果表明，α-Syn小鼠的高脂饮食为评估代谢功能障碍的潜在机制及其对PD患者体重减轻和疾病进展的影响提供了一个敏感工具。此外，还提出嗅觉功能障碍在PD相关的非故意性体重减轻中起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1278/12022322/3a6e57de05ad/41531_2025_961_Fig12_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1278/12022322/3a6e57de05ad/41531_2025_961_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1278/12022322/39e216c388fb/41531_2025_961_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1278/12022322/968b2fa20a02/41531_2025_961_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1278/12022322/48346c9655d7/41531_2025_961_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1278/12022322/3a0f839f4152/41531_2025_961_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1278/12022322/dbcd3a85bbef/41531_2025_961_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1278/12022322/f0258df1dd3c/41531_2025_961_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1278/12022322/5a1ed55a35c8/41531_2025_961_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1278/12022322/062dcfa3279b/41531_2025_961_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1278/12022322/2635cb21c426/41531_2025_961_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1278/12022322/4455f5176d8c/41531_2025_961_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1278/12022322/3a6e57de05ad/41531_2025_961_Fig12_HTML.jpg

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