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. Vehicle (n = 5; group A [Sham]) or 65 mg/kg of streptozotocin (STZ) (n = 19) were intravenously administered into rats 7 days before grouping. We selected the rats for group B and C (n = 7, for each group) by matching blood glucose and body weight. Group A (Sham) and B (DKD) were given normal feed, while group C (DKD+enarodustat) was given feed mixed with 0.01% (w/w) of enarodustat. Kidney samples were collected 14 days after grouping. Total RNAs from renal cortical tissues were analyzed.