Figure 5.

The proposed mechanism whereby sugar exacerbates renal disease in obese mice. Obesity is associated with intestinal dysfunction and increased permeability/leakiness. In these conditions, for the same exposure to sugar, portal veins and systemic levels of fructose are markedly elevated in obese mice in association with higher fructokinase (KHK) expression in the liver and kidney. Furthermore, renal energy charge and mitochondrial function in obese mice are reduced compared to lean counterparts, and therefore, higher fructose delivery and metabolism in the kidney lead to greater metabolic dysfunction, oxidative stress, and inflammation. This effect induced by dietary liquid sugar is markedly ameliorated when renal fructose metabolism is deleted as it impairs glut5-dependent fructose uptake and reabsorption causing fructosuria.