Department of Surgery, Division of Transplant Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Life Sci. 2016 Jan 1;144:69-79. doi: 10.1016/j.lfs.2015.11.022. Epub 2015 Nov 23.
Dietary restriction (DR) and fasting (FA) induce robust protection against the detrimental effects of renal ischemia-reperfusion injury (I/RI). Several mechanisms of protection have been proposed, such as hormesis. Hormesis is defined as a life-supporting beneficial effect resulting from the cellular responses to single or multiple rounds of (mild) stress. The cold exposure (CE) model is a stress model similar to DR, and has been shown to have hormetic effects and has proved to increase longevity. CE is considered to be the most robust method to increase metabolism through activation of brown adipocytes. BAT has been considered important in etiology of obesity and its metabolic consequences.
Since DR, FA, and CE models are proposed to work through hormesis, we investigated physiology of adipose tissue and effect on BAT in these models and compared them to ad libitum (AL) fed mice. We also studied the differential effect of these stress models on immunological changes, and effect of CE on renal I/RI.
We show similar physiological changes in adiposity in male C57Bl/6 mice due to DR, FA and CE, but the CE mice were not protected against renal I/RI. The immunophenotypic changes observed in the CE mice were similar to the AL animals, in contrast to FA mice, that showed major immunophenotypic changes in the B and T cell development stages in primary and secondary lymphoid organs.
Our findings thus demonstrate that DR, FA and CE are hormetic stress models. DR and FA protect against renal I/IR, whereas CE could not.
饮食限制（DR）和禁食（FA）可强烈抵抗肾缺血再灌注损伤（I/RI）的有害影响。已经提出了几种保护机制，例如应激。应激定义为细胞对单次或多次（轻度）应激的反应产生的支持生命的有益作用。冷暴露（CE）模型是一种类似于 DR 的应激模型，已显示出具有应激作用，并已被证明可以延长寿命。CE 被认为是通过激活棕色脂肪细胞增加新陈代谢的最有效方法。BAT 被认为在肥胖及其代谢后果的发病机制中很重要。
由于 DR、FA 和 CE 模型被认为通过应激起作用，我们研究了这些模型中脂肪组织的生理学及其对 BAT 的影响，并将其与自由进食（AL）喂养的小鼠进行了比较。我们还研究了这些应激模型对免疫变化的差异影响，以及 CE 对肾 I/RI 的影响。
我们显示由于 DR、FA 和 CE，雄性 C57Bl/6 小鼠的脂肪堆积出现相似的生理变化，但 CE 小鼠不能抵抗肾 I/RI。CE 小鼠观察到的免疫表型变化与 AL 动物相似，而与 FA 小鼠相反，FA 小鼠在初级和次级淋巴器官的 B 和 T 细胞发育阶段显示出主要的免疫表型变化。
因此，我们的研究结果表明，DR、FA 和 CE 是应激模型。DR 和 FA 可抵抗肾 I/RI，而 CE 则不能。
