Enarodustat, a hypoxia-inducible factor stabilizer, counteracts the diabetic renal energy metabolism alterations in the early stages of diabetic kidney disease

We analyzed the effects of enarodustat (JTZ-951; HIF stabilizer) on renal energy metabolism in alloxan-induced diabetic mouse model. Transcriptome analysis of renal tissue revealed that genes related to fatty acid metabolism were upregulated in diabetes, whereas genes related to glucose metabolism were upregulated by enarodustat. In addition, genes related to amino acid metabolism were upregulated by diabetes and downregulated by enarodustat. Thus, HIF stabilization counteracts the renal energy metabolism alterations occurring in the early stages of diabetic kidney disease. Vehicle (n = 6; group A [Sham]) or 90 mg/kg of alloxan were intravenously administered into mice 3 days before grouping. We selected the mice for group B and C (n = 9, 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 16 days after grouping. Total RNAs from renal tissues were analyzed.