High-fat diet causes mechanical allodynia in the absence of injury or diabetic pathology.
High-fat diet causes mechanical allodynia in the absence of injury or diabetic pathology.
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DOI：
10.1038/s41598-022-18281-x
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发表时间：
2022-09-01
影响因子：
4.6
通讯作者：
Burton, Michael D.
中科院分区：
文献类型：
--
作者：
Tierney, Jessica A.;Uong, Calvin D.;Lenert, Melissa E.;Williams, Marisa;Burton, Michael D.
了解饮食、肥胖和糖尿病之间的相互作用对于梳理疼痛病理机制非常重要。西方饮食富含脂肪，产生大量的循环生物活性代谢物。然而，没有研究评估在没有肥胖或糖尿病病理的情况下，单独的高脂肪饮食（HFD）如何使个体对非疼痛刺激敏感。为了研究这一点，我们在雄性和雌性小鼠中测试了HFD刺激饮食诱导的痛觉过敏启动或饮食致敏的能力。我们的研究结果显示，8周的HFD并没有改变基线疼痛敏感性，但与鼠粮相比，饲喂HFD的雄性和雌性动物在暴露于阈以下剂量的足底前列腺素E2 （PGE2）时都表现出强烈的机械异常性疼痛。此外，在两性分离的初级感觉神经元中，钙成像显示，与食物相比，HFD诱导辣椒素反应神经元的百分比增加。免疫组化（IHC）结果显示，hfd诱导腰背根神经节（DRG）神经元损伤标志物ATF3表达上调。这表明，在没有预先存在的疾病或通过饮食成分受伤的情况下，HFD会引起异常性疼痛。有了对HFD如何导致疼痛发作的新认识，我们就能理解与肥胖和糖尿病相关的合并症背后的分离，从而开发出更有效的药物干预措施。
Understanding the interactions between diet, obesity, and diabetes is important to tease out mechanisms in painful pathology. Western diet is rich in fats, producing high amounts of circulating bioactive metabolites. However, no research has assessed how a high-fat diet (HFD) alone may sensitize an individual to non-painful stimuli in the absence of obesity or diabetic pathology. To investigate this, we tested the ability of a HFD to stimulate diet-induced hyperalgesic priming, or diet sensitization in male and female mice. Our results revealed that 8 weeks of HFD did not alter baseline pain sensitivity, but both male and female HFD-fed animals exhibited robust mechanical allodynia when exposed to a subthreshold dose of intraplantar Prostaglandin E2 (PGE2) compared to mice on chow diet. Furthermore, calcium imaging in isolated primary sensory neurons of both sexes revealed HFD induced an increased percentage of capsaicin-responsive neurons compared to their chow counterparts. Immunohistochemistry (IHC) showed a HFD-induced upregulation of ATF3, a neuronal marker of injury, in lumbar dorsal root ganglia (DRG). This suggests that a HFD induces allodynia in the absence of a pre-existing condition or injury via dietary components. With this new understanding of how a HFD can contribute to the onset of pain, we can understand the dissociation behind the comorbidities associated with obesity and diabetes to develop pharmacological interventions to treat them more efficiently.
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影响因子：
6
作者：
Malesza IJ;Malesza M;Walkowiak J;Mussin N;Walkowiak D;Aringazina R;Bartkowiak-Wieczorek J;Mądry E
通讯作者：
Mądry E
影响因子：
7.6
作者：
Diogenes, A.;Ferraz, C. C. R.;Hargreaves, K. M.
通讯作者：
Hargreaves, K. M.
影响因子：
4
作者：
Carta G;Murru E;Banni S;Manca C
通讯作者：
Manca C
影响因子：
4.1
作者：
Lenert ME;Chaparro MM;Burton MD
通讯作者：
Burton MD
影响因子：
3.6
作者：
Ernsberger, Uwe
通讯作者：
Ernsberger, Uwe