Effect of Folate Status on High‐Fat Diet‐Induced Obese Mice with Chronic Aristolochic Acid Nephropathy

A negative correlation has been reported between human serum folate levels and chronic kidney failure. Reducing folate intake in modern diets high in fat/calories along with low vegetables/fruits might be associated with increased risk for kidney disease in industrialized countries without folic acid fortification policy. To investigate whether folate status affects renal function in high‐fat diet‐induced obesity, four groups of C57BL/6 male mice were either fed normal‐fat diet with folate (NF‐f1) as negative control, or high‐fat diet without folate (HF‐f0), with folate (HF‐f1), with 10‐fold folate (HF‐f10). After 48 weeks' feeding, the HF groups obese mice were supplemented with 8 mg/Kg/day aristolochic acid (AA), a nitrophenanthrene carboxylic acid found in Aristolochic species used in the practice of traditional Chinese medicine, for 3 weeks to induce AA nephropathy (AAN) before sacrifice. The results showed that urine protein of mice fed AA‐containing diets, except the HF‐f10 group, significantly increased. Serum and renal galactin‐3, renal IL‐6 and TNF‐a in obese mice with chronic AAN were significantly higher when compared to the NF‐f1 mice without AA induction. The HF‐f10 mice had lower serum creatinine and higher IL‐10 secretion from ConA‐stimulated splenocytes. In contrast, the HF‐f0 mice had significantly higher urine protein, serum galaction‐3 and IL‐6, renal TGF‐b, and IL‐2 and TGF‐b secretion from splenocytes. Serum folate levels were negatively correlated with renal IL‐6, IL‐1b, TNF‐a, and IL‐10 in the HF‐f0 mice. Our study suggested that folate deficiency might promote, but folate supplementation might protect from renal inflammation and fibrosis progression in high‐fat diet‐induced obese mice. Support or Funding Information Funded by the Ministry of Science and Technology Science Council of the Republic of China [MOST105‐2320‐B‐002‐028‐MY3]