What question did this study set out to answer?

To determine how folate status and fructose intake affect kidney health in a mouse model of chronic kidney disease.

January 6, 2026Open Access

Effects of Folate and Fructose Intakes on Renal Cytokines and Fibrosis in an Adenine-Induced Mouse Model of Chronic Kidney Disease

Key Points

To determine how folate status and fructose intake affect kidney health in a mouse model of chronic kidney disease.
C57BL/6 mice were fed six different diets including various fructose and folate levels.
Mice underwent a treatment involving adenine to induce chronic kidney disease for 7 weeks.
Renal health was assessed by measuring biochemical markers and gene expression related to kidney injury.
Adenine treatment led to increased blood glucose and renal injury markers in all adenine-fed groups.
High fructose diet without sufficient folate resulted in the most severe kidney damage.
Folate supplementation significantly improved renal health, raising IL-10 levels while reducing injury markers.

Abstract

Dietary pattern characterized by low intake of vegetables and fruits and high consumption of fat, soft drink and desserts are associated with an increased risk of chronic diseases. To investigate the effects of folate status and fructose intake on adenine-induced chronic kidney disease (CKD), seven-week-old C57BL/6 mice were divided into six groups and fed either a control diet (Ctrl), a 26% (w/w) high-fructose diet (Hfru), Ctrl plus 0.15% adenine (Ctrl+ade), Hfru+ade, Hfru with folate deficiency plus adenine (Hfru−f+ade), or Hfru with tenfold folate supplementation plus adenine (Hfru+f10+ade). After 10 weeks on the assigned diets, adenine was administrated to the +ade groups for 7 weeks. The results showed that all adenine-treated mice exhibited increased fasting blood glucose, urinary glucose, and elevated renal expression of collagen 1a1 (Col1a1), fibronectin (Fn1), and smooth muscle α-actin (Acta2). Compared with Ctrl mice, Hfru-fed mice showed significantly higher serum creatinine, increased urinary protein, and reduced creatinine clearance. Adenine induced kidney injury in all +ade groups, with the most severe damage observed in Hfru−f+ade mice, as indicated by elevated blood urine nitrogen (BUN), urinary protein, neutrophil gelatinase-associated lipocalin (NGAL), and renal fibrosis. In contrast, Hfru+f10+ade mice showed the lowest levels of these renal injury markers. The Hfru+ade diets increased renal Hif1a and iNos gene expression, which was further exacerbated by folate deficiency. Secretion of the anti-inflammatory cytokine interleukin (IL-10) by splenocytes was significantly reduced under folate-deficient conditions. Renal IL-10 levels were suppressed in all +ade groups but were significantly increased by folate supplementation. Renal IL-10 levels were negatively correlated with the inflammatory chemokine monocyte chemoattractant protein (MCP-1) and transforming growth factor (TGF)-β, whereas renal MCP-1 levels showed positive correlations with TGF-β and IL-6. Overall, these findings suggest that high fructose consumption in the absence of adequate folate intake may be of concern for CKD progression.

Read Full Paperexternally

Mark Helpful

Bookmark

Relay

View Full Paper