Effect of Fasted and Fed Conditions of Protein Turnover in Perfused Cultured Hepatocytes

In vivo studies of protein turnover in the fasted to fed transition have shown conflicting results. In the present study, protein turnover was investigated in primary cultures of rat hepatocytes, perfused for 48 h under conditions simulating portal vein concentrations of amino acids and hormones in the fasted or fed state. The rate of protein degradation was about 40% lower under fed than under fasted conditions. This difference was maintained for 36 h of perfusion. Transition from fasted to fed conditions showed an immediate decrease in the degradation rate to that exhibited by cultures perfused under fed conditions. After 24 h of perfusion, the rate of synthesis was 50% higher with a fed medium, and transition from fasted to fed conditions resulted in a 50% increase in the synthesis rate. Dose-response relationships for insulin showed effects on protein turnover in the insulin concentration range below the physiologic range. It is concluded that protein degradation as well as protein synthesis in the fasted to fed transition is regulated mainly by the amino acid concentrations.