Technetium-99m-GSA clearance in mice under long-term dietary restriction

Dietary restriction (DR) without malnutrition is widely acknowledged to prolong lifespan in laboratory animals. Evidence suggests that DR retards age-related decline in protein turnover of most organs. However, there has been no report about hepatic serum glycoprotein catabolism under DR. In the current study, we evaluate the hepatic uptake of asialoglycoprotein in ICR mice with DR by measuring the plasma clearance of technetium-99m galactosyl human serum albumin (Tc-GSA).

The amount of food supplied to the restricted mice was 70% of that consumed by the mice fed ad libitum (AL). The regimen was initiated at the age of 7 weeks and terminated after the age of 44 weeks. The plasma clearance of Tc-GSA was measured at the age of 7 weeks, 14 weeks, 28 weeks, and 42 weeks.

The restricted animals showed a marked decrease in their body and liver weight, and hepatic uptake of Tc-GSA per liver weight in the restricted mice was greater than that in the mice fed AL. On the other hand, the Tc-GSA plasma clearance in the mice fed AL was stable during the study period, and that in the restricted mice showed no change with age either, and those in the two groups were similar. In addition to the receptor function, there was no difference in the expression of mRNAs of the asialoglycoprotein receptor between the two groups. Serum concentrations of cholinesterase and hepatic mRNAs of glutamine synthetase in the restricted mice were higher than those in the mice fed AL. Serum levels of amino acids in the restricted mice were lower than those in the mice fed AL.

The data presented here show that the DR did not affect the capacity of hepatic serum glycoprotein catabolism, whereas several protein metabolic pathways were affected.