The effect of dietary macronutrients on fenestrations in the aging liver sinusoidal cells

The hepatic sinusoidal endothelium is perforated with fenestrations, which facilitate the transfer of substrates from blood to hepatocytes. Fenestrations number and size are altered in response to dietary manipulations such as... [ view full abstract ]

The hepatic sinusoidal endothelium is perforated with fenestrations, which facilitate the transfer of substrates from blood to hepatocytes. Fenestrations number and size are altered in response to dietary manipulations such as fasting and caloric restriction. Here we determined the effects of exposure to different dietary macronutrients on fenestrations in old age. C57BL/6 male and female mice (n=858) were ad libitum fed 1 of 25 diets varying in protein, carbohydrate, and fat content. At 15 months liver samples were obtained, perfusion-fixed and prepared for scanning electron microscopy using standard method. Average fenestration diameter, frequency and LSEC porosity were calculated for each diet. The effect of macronutrients intake on fenestrations were analyzed using the Geometric Framework approach. Results showed that fenestration porosity was influenced by dietary fat intake (P=0.016), with low to intermediate fat intakes (around 20 kJ/mouse/day) associated with highest porosity. This is parallel to the response of fenestration frequency that is being associated only with fat intake (P=0.001). In addition, fenestration frequency was inversely associated with protein and carbohydrate intakes (P=0.028 and P=0.006, respectively). Low carbohydrate or low protein intake were both associated with increased fenestration diameter. These findings indicate that macronutrients had complex effects on LSEC fenestrations, with reduced intake of macronutrients was associated with increased fenestration frequency and/or diameter, and fat having the dominant influence on porosity. This reveals the potential interventions linking fenestrations and diet on liver health in aging.