Investigating the Role of Metabolic Reprogramming in the Pathogenesis of Diabetic Kidney Disease Using Novel Metabolic Mouse Models

Metabolic disorders are involved in the pathogenesis of diabetic kidney disease (DKD), and protein lipoylation may regulate metabolic disorders and energy reprogramming in DKD. To elucidate the role of protein lipoylation in metabolic regulation and understand its underlying mechanism, we used the Ins2Akita, a diabetic mouse model, crossed with lipoic acid synthase transgenic mice to illustrate the role of metabolic regulation at the initiation and early stages of DKD. We found that enhanced protein lipoylation attenuates the early DKD phenotype by analyzing renal albuminuria, glomerular mesangial expansion, and mitochondrial damage in proximal tubular epithelial cells as the LiasH/HIns2Akita/+ mice had markedly milder DKD phenotype than LiasL/LIns2Akita/+ mice via metabolic regulation by protein lipoylation. These data suggest that enhanced protein lipoylation potentially attenuates DKD by regulating metabolism and energy reprogramming. Our study provides insight into a new therapeutic strategy for DKD.

The data included is high resolution mass spectrometry metabolomics raw data (generated on a Thermo Q Exactive HF-X). A processed peak list is also included along with metabolites that were identified in the samples.