肥胖成像的前景:[18F]2FNQ1P--一种特异性 5-HT6 脑 PET 放射性示踪剂。

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM International Journal of Obesity Pub Date : 2024-10-07 DOI:10.1038/s41366-024-01644-x
Pierre Courault, Sandrine Bouvard, Caroline Bouillot, Radu Bolbos, Waël Zeinyeh, Thibaut Iecker, François Liger, Thierry Billard, Luc Zimmer, Fabien Chauveau, Sophie Lancelot
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引用次数: 0

摘要

背景:据估计,到 2025 年,全球约有 25% 的人口将超重。更好地了解肥胖症的病理生理学有助于开发未来的治疗方法。研究表明,5-羟色胺亚型 6 受体(5-HT6)在降低食欲和减轻体重方面发挥着关键作用。然而,肥胖引发的病理级联是否会改变大脑中5-HT6受体的密度尚不清楚:方法:使用核磁共振成像(全身脂肪)和正电子发射计算机断层扫描([18F]2FNQ1P 作为特异性 5-HT6 放射性示踪剂)研究了饮食诱导肥胖(DIO)对 Wistar 大鼠的影响。主要目的是监测大鼠在 10 周饮食(DIO 组)前后的 5-HT6 受体密度。次要目标是比较 DIO 组、Wistar 对照饮食组、Zucker 大鼠(遗传性肥胖)和 Zucker 瘦株大鼠的 5-HT6 受体密度:结果:以高脂饮食喂养的 Wistar 大鼠在核磁共振成像上的体脂增加率高于 Wistar 对照饮食大鼠。[18F]2FNQ1P正电子发射计算机断层扫描分析显示,在高脂饮食后,海马、纹状体、扣带回、颞叶皮层和脑干等部位的体素结合率明显增加(p 结论:该研究对肥胖大鼠的体素结合率进行了分析:本研究揭示了高脂饮食对 5-HT6 受体的影响。这项研究还将[18F]2FNQ1P PET定位为探索肥胖或饮食失调病理生理学对神经元影响的创新工具。
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Perspectives on obesity imaging: [18F]2FNQ1P a specific 5-HT6 brain PET radiotracer.

Background: Estimates suggest that approximatively 25% of the world population will be overweight in 2025. Better understanding of the pathophysiology of obesity will help to develop future therapeutics. Serotonin subtype 6 receptors (5-HT6) have been shown to be critically involved in appetite reduction and weight loss. However, it is not known if the pathological cascade triggered by obesity modifies the density of 5-HT6 receptors in the brain.

Methods: Influence of diet-induced obesity (DIO) in Wistar rats was explored using MRI (whole-body fat) and PET ([18F]2FNQ1P as a specific 5-HT6 radiotracer). The primary goal was to monitor the 5-HT6 receptor density before and after a 10-week diet (DIO group). The secondary goal was to compare 5-HT6 receptor densities between DIO group, Wistar control diet group, Zucker rats (with genetic obesity) and Zucker lean strain rats.

Results: Wistar rats fed with high-fat diet showed higher body fat gain than Wistar control diet rats on MRI. [18F]2FNQ1P PET analysis highlighted significant clusters of voxels (located in hippocampus, striatum, cingulate, temporal cortex and brainstem) with increased binding after high-fat diet (p < 0.05, FWE corrected).

Conclusion: This study sheds a new light on the influence of high-fat diet on 5-HT6 receptors. This study also positions [18F]2FNQ1P PET as an innovative tool to explore neuronal consequences of obesity or eating disorder pathophysiology.

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来源期刊
International Journal of Obesity
International Journal of Obesity 医学-内分泌学与代谢
CiteScore
10.00
自引率
2.00%
发文量
221
审稿时长
3 months
期刊介绍: The International Journal of Obesity is a multi-disciplinary forum for research describing basic, clinical and applied studies in biochemistry, physiology, genetics and nutrition, molecular, metabolic, psychological and epidemiological aspects of obesity and related disorders. We publish a range of content types including original research articles, technical reports, reviews, correspondence and brief communications that elaborate on significant advances in the field and cover topical issues.
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