Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 37, 50937 Cologne, Germany.
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Joseph-Stelzmann-Straße 26, 50931 Cologne, Germany.
Int J Mol Sci. 2021 May 22;22(11):5485. doi: 10.3390/ijms22115485.
Acute kidney injury (AKI) is a frequent and critical complication in the clinical setting. In rodents, AKI can be effectively prevented through caloric restriction (CR), which has also been shown to increase lifespan in many species. In (), longevity studies revealed that a marked CR-induced reduction of endocannabinoids may be a key mechanism. Thus, we hypothesized that regulation of endocannabinoids, particularly arachidonoyl ethanolamide (AEA), might also play a role in CR-mediated protection from renal ischemia-reperfusion injury (IRI) in mammals including humans. In male C57Bl6J mice, CR significantly reduced renal IRI and led to a significant decrease of AEA. Supplementation of AEA to near-normal serum concentrations by repetitive intraperitoneal administration in CR mice, however, did not abrogate the protective effect of CR. We also analyzed serum samples taken before and after CR from patients of three different pilot trials of dietary interventions. In contrast to mice and , we detected an increase of AEA. We conclude that endocannabinoid levels in mice are modulated by CR, but CR-mediated renal protection does not depend on this effect. Moreover, our results indicate that modulation of endocannabinoids by CR in humans may differ fundamentally from the effects in animal models.
急性肾损伤（AKI）是临床中的一种常见且严重的并发症。在啮齿动物中，通过热量限制（CR）可以有效地预防 AKI，并且已经在许多物种中显示出可以延长寿命。在（）中，长寿研究表明，内源性大麻素的显著减少可能是关键机制。因此，我们假设内源性大麻素的调节，特别是花生四烯酰乙醇胺（AEA），也可能在哺乳动物（包括人类）的 CR 介导的肾缺血再灌注损伤（IRI）保护中发挥作用。在雄性 C57Bl6J 小鼠中，CR 显著降低了肾 IRI，并导致 AEA 显著减少。然而，通过在 CR 小鼠中重复腹腔内给药将 AEA 补充到接近正常的血清浓度，并没有消除 CR 的保护作用。我们还分析了来自三种不同饮食干预初步试验的患者在 CR 前后的血清样本。与小鼠和（）相反，我们检测到 AEA 增加。我们得出结论，CR 调节了小鼠的内源性大麻素水平，但 CR 介导的肾脏保护不依赖于这种作用。此外，我们的结果表明，CR 在人类中对内源性大麻素的调节可能与动物模型中的作用有根本的不同。
