Comparison of western diet-induced obesity and streptozotocin mouse models: insights into energy balance, somatosensory dysfunction, and cardiac autonomic neuropathy.
Comparison of western diet-induced obesity and streptozotocin mouse models: insights into energy balance, somatosensory dysfunction, and cardiac autonomic neuropathy.
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西方饮食诱导的肥胖症和链霉菌素小鼠模型的比较：对能量平衡，体感功能障碍和心脏自主神经神经病的见解。
DOI：
10.3389/fphys.2023.1238120
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发表时间：
2023
影响因子：
4
通讯作者：
中科院分区：
文献类型：
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作者：
代谢性疾病，如肥胖和2型糖尿病（T2D）在世界范围内日益普遍，需要更深入地了解其潜在机制。然而，将动物研究结果转化为人类患者仍然具有挑战性。本研究旨在探讨低剂量链脲佐菌素（STZ）对高脂肪、高蔗糖和高胆固醇西方饮食（WD）小鼠代谢、心脏和体感功能的长期影响。在我们的研究中，我们彻底地描述了能量平衡和葡萄糖稳态，以及异常性疼痛和心功能，所有这些都被证明是由WD喂养改变的。值得注意的是，我们的研究结果显示，除了外周胰岛素信号通路受损外，用wd喂养的STZ小鼠通过减少胰岛素分泌加剧了葡萄糖稳态功能障碍。此外，WD和WD + STZ小鼠均表现出相同程度的心脏自主神经病变，如心率变异性降低和心脏自主神经标志物蛋白水平降低。此外，两组均出现相同的神经性疼痛症状，并伴有背根神经节中激活转录因子3 （Atf3）水平升高。这些发现增强了我们对饮食诱导的肥胖和糖尿病模型的代谢活动、胰岛素抵抗、神经病变和心功能障碍的理解。STZ对胰岛素信号通路损伤的加剧不导致或加重心脏和躯体感觉功能障碍。此外，它们为适当的饮食诱导的翻译小鼠模型提供了有价值的见解，从而促进了相关疾病潜在干预措施的发展。
Metabolic disorders such as obesity and type 2 diabetes (T2D) are increasingly prevalent worldwide, necessitating a deeper comprehension of their underlying mechanisms. However, translating findings from animal research to human patients remains challenging. This study aimed to investigate the long-term effects of Streptozotocin (STZ) on metabolic, cardiac, and somatosensory function in mice fed a Western diet (WD) of high fat, sucrose, and cholesterol with low doses of STZ administration compared to mice fed WD alone. In our research, we thoroughly characterized energy balance and glucose homeostasis, as well as allodynia and cardiac function, all of which have been previously shown to be altered by WD feeding. Notably, our findings revealed that the treatment of WD-fed mice with STZ exacerbated dysfunction in glucose homeostasis via reduced insulin secretion in addition to impaired peripheral insulin signaling. Furthermore, both WD and WD + STZ mice exhibited the same degree of cardiac autonomic neuropathy, such as reduced heart rate variability and decreased protein levels of cardiac autonomic markers. Furthermore, both groups developed the same symptoms of neuropathic pain, accompanied by elevated levels of activating transcription factor 3 (Atf3) in the dorsal root ganglia. These discoveries enhance our understanding of metabolic activity, insulin resistance, neuropathy, and cardiac dysfunction of diet-induced models of obesity and diabetes. The exacerbation of impaired insulin signaling pathways by STZ did not lead to or worsen cardiac and somatosensory dysfunction. Additionally, they offer valuable insights into suitable diet induced translational mouse models, thereby advancing the development of potential interventions for associated conditions.
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影响因子：
4.2
作者：
Duque A;Mediano MFF;De Lorenzo A;Rodrigues LF Jr
通讯作者：
Rodrigues LF Jr
影响因子：
20.1
作者：
Fukuda K;Kanazawa H;Aizawa Y;Ardell JL;Shivkumar K
通讯作者：
Shivkumar K
影响因子：
3.7
作者：
Vitzel KF;Bikopoulos G;Hung S;Curi R;Ceddia RB
通讯作者：
Ceddia RB
影响因子：
9.3
作者：
Thackeray JT;Radziuk J;Harper ME;Suuronen EJ;Ascah KJ;Beanlands RS;Dasilva JN
通讯作者：
Dasilva JN
影响因子：
--
作者：
Agashe, Shruti;Petak, Steven
通讯作者：
Petak, Steven