在改良细菌饮食条件下，阿米替林通过prdx-2增加线虫的食物摄入量，而不改变其他生理参数。

Amitriptyline increases food intake via prdx-2 without altering other physiological parameters in C. elegans under a modified bacterial diet.

Almotayri Abdullah M, Alghamdi Abdullah A A, Almimoni Nourah M, Alghamdi Thamer H, Alzahrani Magbolah S, Elsherbiny K, Alghamdi Ali H

Department of Biology, Faculty of Science, Al-Baha University, Al-Baha, Saudi Arabia.

College of Medicine, Al-Baha University, Al-Baha, Saudi Arabia.

Sci Rep. 2025 Aug 11;15(1):29428. doi: 10.1038/s41598-025-14773-8.

Abstract

Amitriptyline, a tricyclic antidepressant, is associated with various metabolic side effects, including increased appetite and weight gain. In this study, we used the nematode C. elegans to investigate the drug's effects on food intake, fat content, lifespan, and several genetic pathways. Amitriptyline increased food intake in a dose-responsive manner. It increased the food intake primarily through elevated on-food pharyngeal pumping. Supplementation with glucose exacerbated these effects and significantly shortened lifespan, mimicking metabolic risks seen in humans. Despite increased feeding, no changes in fat content were observed, reflecting distinct mechanisms regulating feeding and fat storage. The critical function of prdx-2 in the drug's effect on food intake was revealed through genetic analyses. In contrast, several receptors and signaling components in the serotonergic, dopaminergic, and insulin-like pathways were not implicated. These results underscore the potential of C. elegans as a model for investigating antidepressant-induced metabolic alterations and establish the foundation for strategies to mitigate these effects.

摘要

三环类抗抑郁药阿米替林会引发各种代谢副作用，包括食欲增加和体重上升。在本研究中，我们利用线虫秀丽隐杆线虫来探究该药物对食物摄取、脂肪含量、寿命以及若干基因通路的影响。阿米替林以剂量反应方式增加食物摄取量。它主要通过提高咽部在食物上的抽吸频率来增加食物摄取。补充葡萄糖会加剧这些影响并显著缩短寿命，模拟了人类所见的代谢风险。尽管进食增加，但未观察到脂肪含量的变化，这反映了调节进食和脂肪储存的不同机制。通过基因分析揭示了prdx - 2在该药物对食物摄取影响中的关键作用。相比之下，血清素能、多巴胺能和胰岛素样通路中的几种受体和信号成分未涉及其中。这些结果强调了秀丽隐杆线虫作为研究抗抑郁药诱导的代谢改变模型的潜力，并为减轻这些影响的策略奠定了基础。