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 conditions the in vitro metabolic effects of fructose and insulin on the triglyceride formation by the isolated perfused livers obtained from hypertriglyceridemic rats that had been fed a sucrose-rich diet for a long-term (15 week) period as compared with those fed sucrose for a short-term (3 week) period. Our findings indicate a significantly higher increase in triglyceride formation by perfused livers of rats fed the sucrose-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 elevated 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 triglycerides from livers of animals fed the sucrose diet at both durations of feeding. Despite this finding, long-term sucrose led to even higher hepatic triglyceride storage under the present experimental conditions (micromole/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 liver triglycerides at both durations of feeding on the sucrose rich diet. However, different insulin responses have been observed, showing an increase (3-fold) in triglyceride storage only in rats fed the sucrose diet for 3 weeks and an inhibition (32%) on the net triglyceride output only in animals fed the sucrose diet for 15 weeks. Our findings indicate important differences in the in vitro effects of fructose and insulin on hepatic triglyceride formation characterized by an imbalance between secretion and storage depending on the duration of feeding on the sucrose-rich diet. Thus care should be taken when generalizing conclusions on the effects of nutrients or hormones in this nutritionally induced hyperlipemic experimental animal model, since variable metabolic milieu may emerge at different durations of feeding on the diet.