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

作者：Huiru Yang, Xiaoli Yi, Shanshan Song, Mulan Wang, Wenting Tan, Ying Zhu, Jun Yu, Chuanming Xu · 发表于：Acta Biochimica et Biophysica Sinica · 年份：2025 · DOI：10.3724/abbs.2025191 · 被引用次数：5 · 研究领域：Diet, Metabolism, and Disease、Liver Disease Diagnosis and Treatment、Diet and metabolism studies

The liver is a crucial site for fructose uptake and metabolism, a function intricately linked to fructose-associated pathologies. This study examines the role of hepatic ketohexokinase (KHK) in metabolic syndrome induced solely by high-fructose intake. Liver-specific Khk -deficient mice are generated and fed a 20% fructose solution for 3 months, after which the features of metabolic syndrome are examined. Compared with fructose-fed floxed controls, fructose-fed liver-specific Khk -deficient mice present alleviated liver injury and hepatic steatosis, along with lower triglyceride levels in the plasma and liver, plasma aspartate transaminase and alanine transaminase levels, and mRNA levels of genes related to triglyceride and fatty acid synthesis. Liver-specific Khk deficiency also leads to lower uric acid levels in the plasma and urine, as well as xanthine oxidase activity and Glut9 mRNA levels in the liver and kidneys of fructose-fed mice. Although intestinal villus length and epithelial barrier integrity remain unaffected, the deletion of liver Khk significantly reduces fructose-stimulated KHK, Glut2, Glut5, and aldolase B expression in the intestine and kidneys, suggesting inhibited fructose absorption and metabolism in these tissues. In the adipose tissue, fructose-induced increases in adipocyte size and tumor necrosis factor-α and interleukin-6 mRNA levels are blocked by liver-specific Khk deficiency, indicating improved remodeling of adipose tissue and reduce...