The effect of liver-specific ketohexokinase deletion on the intestinal-liver-kidney axis in high-fructose-induced metabolic syndrome mice

• Liver-specific KHK deletion alleviates hepatic steatosis and injury in high-fructose-fed mice, reducing plasma and liver triglycerides and key enzyme markers. • Hepatic KHK deficiency lowers uric acid levels and xanthine oxidase activity in plasma, urine, liver, and kidneys, indicating systemic metabolic benefits. • Deletion of liver KHK reduces fructose-stimulated expression of fructose transporters and metabolizing enzymes in intestine and kidneys, suggesting inhibited fructose absorption and metabolism. • Liver-specific KHK deletion improves adipose tissue remodeling and reduces inflammation, protecting against fructose-induced metabolic syndrome.