Energy insufficiency induced by high purine diet: Catalysts for renal impairment in hyperuricemia nephropathy rat model

Abstract

A high purine diet emerges as a significant risk factor for hyperuricemia, and this diet may potentiate hyperuricemia nephropathy. Despite this, the mechanistic underpinnings of kidney damage precipitated by a high purine diet warrant further research. In the current investigation, a hyperuricemia nephropathy rat model was developed through induction via a high purine diet. Subsequently, metabolomic and proteomic analyses were employed to explore the metabolic characteristics of the kidney and shed light on the corresponding mechanistic pathway. Finally, fluorescence imaging and 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG-PET/CT) were utilized to validate the overarching energy metabolism state. The results revealed extensive damage to the kidneys of hyperuricemia nephropathy rats following eight weeks of induction via a high purine diet. We used metabolomic to found that acyl carnitines and L-carnitine reduced in high purine diet group, indicated abnormal fatty acid metabolism. Irregularities were discerned in metabolites and enzymes associated with fatty acid β-oxidation, glycolysis, and oxidative phosphorylation within the kidneys of hyperuricemia nephropathy rats by proteomic and co-expression network analysis. The application of fluorescence imaging and 18F-FDG-PET/CT substantiated the inhibition of fatty acid β-oxidation and glycolysis within the kidneys of hyperuricemia nephropathy rats. On the contrary, a compensatory enhancement in the function of oxidative phosphorylation was observed. Given that the primary energy supply for renal function was derived from the metabolic pathway of fatty acids β-oxidation, any disruption within this pathway could contribute to a deficit in the energy provision to the kidneys. Such an energy insufficiency potentially laid the groundwork for eventual renal impairment. In addition, inhibition of the peroxisome proliferator-activated receptors signaling pathway was noted in the present findings, which could further exacerbate the impediment in the β-oxidation function. In conclusion, it was discerned that a deficiency in energy supply plays a critical role in the kidney injury in hyperuricemia nephropathy rats, thereby endorsing paying more attention to renal energy supply in the therapy of hyperuricemia nephropathy.