Institute of Medical Sciences, University of Aberdeen, College of Life Sciences and Medicine, Foresterhill Health Campus, Aberdeen, UK.
Institute of Medical Sciences, University of Aberdeen, College of Life Sciences and Medicine, Foresterhill Health Campus, Aberdeen, UK; Liverpool Hope University, Liverpool, UK.
Mech Ageing Dev. 2016 Jul;157:35-43. doi: 10.1016/j.mad.2016.07.003. Epub 2016 Jul 21.
Dietary methionine restriction (MR) leads to loss of adiposity, improved insulin sensitivity and lifespan extension. The possibility that dietary MR can protect the kidney from age-associated deterioration has not been addressed. Aged (10-month old) male and female mice were placed on a MR (0.172% methionine) or control diet (0.86% methionine) for 8-weeks and blood glucose, renal insulin signalling, and gene expression were assessed. Methionine restriction lead to decreased blood glucose levels compared to control-fed mice, and enhanced insulin-stimulated phosphorylation of PKB/Akt and S6 in kidneys, indicative of improved glucose homeostasis. Increased expression of lipogenic genes and downregulation of PEPCK were observed, suggesting that kidneys from MR-fed animals are more insulin sensitive. Interestingly, renal gene expression of the mitochondrial uncoupling protein UCP1 was upregulated in MR-fed animals, as were the anti-ageing and renoprotective genes Sirt1, FGF21, klotho, and β-klotho. This was associated with alterations in renal histology trending towards reduced frequency of proximal tubule intersections containing vacuoles in mice that had been on dietary MR for 190days compared to control-fed mice, which exhibited a pre-diabetic status. Our results indicate that dietary MR may offer therapeutic potential in ameliorating the renal functional decline related to ageing and other disorders associated with metabolic dysfunction by enhancing renal insulin sensitivity and renoprotective gene expression.
饮食蛋氨酸限制（MR）会导致肥胖减轻、胰岛素敏感性提高和寿命延长。饮食 MR 是否能保护肾脏免受与年龄相关的恶化，这一可能性尚未得到解决。将老年（10 个月大）雄性和雌性小鼠分别置于 MR（0.172%蛋氨酸）或对照饮食（0.86%蛋氨酸）中 8 周，然后评估血糖、肾脏胰岛素信号和基因表达。与对照喂养的小鼠相比，蛋氨酸限制导致血糖水平降低，并且增强了肾脏中 PKB/Akt 和 S6 的胰岛素刺激磷酸化，表明葡萄糖稳态得到改善。观察到脂肪生成基因的表达增加和 PEPCK 的下调，表明来自 MR 喂养动物的肾脏对胰岛素更敏感。有趣的是，MR 喂养动物的肾脏中线粒体解偶联蛋白 UCP1 的基因表达上调，同时抗衰老和肾脏保护基因 Sirt1、FGF21、klotho 和β-klotho 的基因表达也下调。这与肾脏组织学的改变有关，与对照喂养的小鼠相比，经过 190 天饮食 MR 喂养的小鼠的近端肾小管交点中含有空泡的频率趋势降低，而对照喂养的小鼠表现出糖尿病前期状态。我们的结果表明，饮食 MR 通过增强肾脏胰岛素敏感性和肾脏保护基因表达，可能为改善与衰老相关的肾脏功能下降和其他与代谢功能障碍相关的疾病提供治疗潜力。
