Folate Deficiency Enhanced Inflammation and Exacerbated Renal Fibrosis in High-Fat High-Fructose Diet-Fed Mice

Area of Science:

• Nephrology
• Nutritional Science
• Metabolic Disease Research

Background:

• Obesity and chronic kidney disease (CKD) are rising globally.
• Previous research linked folate deficiency to increased adipocyte lipid accumulation and leptin production.
• The role of folate in obesity-related nephropathy remained unclear.

Purpose of the Study:

• To investigate the impact of folate deficiency on diet-induced obesity and CKD in mice.
• To explore the mechanisms by which folate deficiency affects renal inflammation and fibrosis.

Main Methods:

• Male C57BL/6 mice were fed normal-fat (NF) or high-fat high-fructose (HFF) diets, with or without folate, for 12 months.
• Key metabolic parameters, cytokine levels, kidney function markers, and renal fibrosis indicators were assessed.
• Phosphorylation of pro-fibrosis signaling molecules (STAT3, Smad2/3) was analyzed.

Main Results:

• HFF diet increased body weight, blood glucose, lipids, blood pressure, pro-inflammatory cytokines, and kidney damage markers.
• Folate deficiency exacerbated these effects, increasing serum lipids, specific cytokines (IL-6, TNF-α, MCP-1, TGF-β1), leptin, and renal fibrosis.
• Both HFF and folate deficiency significantly increased STAT3 and Smad2/3 phosphorylation, indicating synergistic effects on renal inflammation and fibrosis.

Conclusions:

• Folate deficiency aggravates the inflammatory status in diet-induced obese mice.
• Folate deficiency enhances renal fibrosis, potentially through increased STAT3 and Smad2/3 signaling.
• Maintaining adequate folate levels may be crucial for mitigating kidney damage in obesity-related conditions.