Hiromichi Komatsu

Effect of Valine-Depleted Total Parenteral Nutrition on Fatty Liver Development in Tumor-Bearing Rats

Valine-depleted amino acid imbalance, while having a suppressive effect on tumor growth, may induce fatty liver. We administered valine-depleted total parenteral nutrition (TPN) solution to rats subcutaneously transplanted with ascites containing hepatoma AH-109A and examined the time course of the development of fatty liver. An accumulation of fatty vacuoles was observed in hepatocytes on day 4. To prevent the development of fatty liver in tumor-bearing rats, we administered a small amount of valine in addition to the valine-depleted imbalance solution via the central vein. Such treatment, however, resulted in neither the prevention of fatty liver development nor the suppression of tumor growth. To supply valine to the liver, we administered a low concentration of valine via the portal vein simultaneously with central venous administration of valine-depleted TPN solution. As a result, the peripheral blood valine level of these rats was < 0.5 that of the control group, but the valine in the liver was maintained at the same level as that of the control group, and accumulation of triacylglycerols in the liver was slight. However, the suppressive effect on tumor growth was maintained, as the tumor weight was suppressed to almost the same degree as that of rats administered only the valine-depleted solution.

Prevention of fatty liver and maintenance of systemic valine depletion using a newly developed dual infusion system.

BACKGROUND Valine-depleted amino acid imbalance, while having a suppressive effect on tumor growth, may induce fatty liver. METHODS We administered a valine-depleted total parenteral nutrition (TPN) solution by the central venous route to non-tumor-bearing rats and examined the time course of the development of fatty liver. In an attempt to prevent this condition, we administered a continuous infusion of low concentrations of valine via the portal vein simultaneously with administration of central venous valine-depleted nutrition for 4 days. RESULTS A marked accumulation of triglyceride was observed in the liver on day 4 of the administration of valine-depleted nutrition. It is speculated that such accumulation is the cause of fatty liver. The level of valine in the peripheral blood began to decrease soon after administration was begun and resulted in a state of systemic valine deficiency. Rats given 25% or more of the valine concentration in the standard TPN solution via the portal vein simultaneously with the administration of central venous valine-depleted nutrition, had a triglyceride level similar to that of the control group. The group given 50% or less of the valine concentration had a level of valine in the peripheral blood as low as that of the valine-depleted group, indicating the maintenance of a valine-deficient state. CONCLUSION Administration of low concentrations of valine via the portal vein simultaneous with central venous administration of valine-depleted TPN solution may prevent fatty liver.

Effects of caloric intake on anticancer therapy in rats with valine‐depleted amino acid imbalance

Valine-depleted amino acid imbalance solution markedly inhibits tumor growth but causes fatty liver as a side effect. However, much remains unknown about the mechanism of the development of fatty liver. Valine-depleted amino acid imbalance solution containing various concentrations of calories was administered to tumor-bearing rats for four days by means of total parenteral nutritional methods to investigate the interaction of caloric intake and the development of fatty liver. Compared with the total parenteral nutrition control group the triglyceride content of the liver rose significantly in the group given valine-depleted amino acid imbalance solution with an increase in caloric intake. Plasma total protein and albumin significantly decreased. The very-low-density lipoprotein concentration in serum was also significantly lower than that in the control group. Valine-depleted amino acid imbalance caused hypoproteinemia, suggesting a fall in synthesis of apolipoproteins in the liver indispensable for lipid release. Along with the increase in the total caloric intake, triglyceride synthesis in the liver increased, resulting in augmentation of fatty content of the liver, probably because of the decreased lipid release.