THE DURATION OF FEEDING ON A SUCROSE-RICH DIET DETERMINES VARIABLE IN-VITRO EFFECTS OF INSULIN AND FRUCTOSE ON RAT-LIVER TRIGLYCERIDE-METABOLISM

The aim of the present study was to investigate under controlled condi tions the in vitro metabolic effects of fructose and insulin on the tr iglyceride formation by the isolated perfused livers obtained from hyp ertriglyceridemic rats that had been fed a sucrose-rich diet for a lon g-term (15 week) period as compared with those fed sucrose for a short -term (3 week) period. Our findings indicate a significantly higher in crease in triglyceride formation by perfused livers of rats fed the su crose-rich diet for a long-term period in the presence of oleate as a triglyceride-forming substrate (15 weeks, 6-fold increase; 3 weeks, 2- fold increase). Though the contribution of net triglyceride secretion to this increase in triglyceride formation was about twice as high at both durations of feeding on a sucrose-rich diet, a strikingly elevate d liver triglyceride accumulation was recorded for a long-term period (15 week, 10-fold increase; 3 week, 4-fold increase). The addition of fructose in the perfusate further increased the output of triglyceride s from livers of animals fed the sucrose diet at both durations of fee ding. Despite this finding, long-term sucrose led to even higher hepat ic triglyceride storage under the present experimental conditions (mu mol/liver at 15 week; 318.2 +/- 17.2 vs. 63.0 +/- 10.0 at 3 week; P < 0.001). Insulin in the presence of fructose promoted synthesis of live r triglycerides at both durations of feeding an the sucrose-rich diet. However, different insulin responses have been observed, showing an i ncrease (3-fold) in triglyceride storage only in rats fed the sucrose diet for 3 weeks and an inhibition (32%) on the net triglyceride outpu t only in animals fed the sucrose diet for 15 weeks. Our findings indi cate important differences in the in vitro effects of fructose and ins ulin on hepatic triglyceride formation characterized by an imbalance b etween secretion and storage depending on the duration of feeding on t he sucrose-rich diet. Thus care should be taken when generalizing conc lusions on the effects of nutrients or hormones in this nutritionally induced hyperlipemic experimental animal model, since variable metabol ic milieu may emerge at different durations of feeding on the diet.