Enarodustat, hypoxia-inducible factor stabilizer, counteracts the diabetic renal energy metabolism alterations in streptozotocin-induced diabetic rats

We analyzed the effects of enarodustat (JTZ-951; HIF stabilizer) on renal energy metabolism in streptozotocin-induced diabetic rat model. Transcriptome analysis of renal cortex revealed that genes related to fatty acid metabolism and amino acid metabolism were upregulated in diabetes and downregulated by enarodustat, whereas genes related to glucose metabolism were upregulated by enarodustat. Thus, HIF stabilization counteracts the renal energy metabolism alterations occurring in the early stages of diabetic kidney disease.本研究分析了埃纳罗司他（enarodustat，JTZ-951，缺氧诱导因子（Hypoxia-Inducible Factor，HIF）稳定剂）对链脲佐菌素（streptozotocin）诱导的糖尿病大鼠模型肾脏能量代谢的影响。对肾皮质开展转录组分析（Transcriptome analysis）后结果显示：糖尿病状态下，脂肪酸代谢与氨基酸代谢相关基因的表达量显著上调，而经埃纳罗司他处理后此类基因的表达被下调；与之相反，糖代谢相关基因的表达则因埃纳罗司他处理而上调。综上，缺氧诱导因子（HIF）稳定化可抵消糖尿病肾病早期阶段出现的肾脏能量代谢异常。