INHIBITION OF HEPATIC VERY-LOW-DENSITY LIPOPROTEIN SECRETION IN OBESE ZUCKER RATS ADAPTED TO A HIGH-PROTEIN DIET

The effect of a high-protein (HP) diet on hepatic very-low density lipoprotein (VLDL) secretion was studied in obese and lean Zucker rats. With the control (C) diet, isolated hepatocytes from obese as compared with lean rats displayed higher uptake of [1-C-14]oleate 0.7 mmol/L, 95% of which was esterified to glycerolipids; greater oleate incorporation into VLDL-triacylglycerol (TG); 2.6 times higher total VLDL-TG secretion; and Ii-fold higher de novo fatty acid synthesis. Adaptation to HP feeding decreased weight gains in both phenotypes and hepatocyte TG content in obese rats. Oleate uptake by hepatocytes was appreciably reduced in the obese phenotype only. Despite esterification rates similar to those for the C diet, oleate incorporation into VLDL-TG decreased by 34% and 55% in obese and lean rats, respectively. Total (mass) VLDL-TG secretion was drastically decreased by 65% and 48% in obese and lean rat hepatocytes, respectively. HP feeding combined with overnight fasting accentuated the above decreases. Fatty acid synthesis was 50% lower in cells from HP-fed obese rats, but increased 1.7-fold in lean ones. Plasma glucagon increased in both phenotypes under HP feeding, whereas plasma insulin either increased (obese) or decreased (lean), with the insulin to glucagon ratio slightly decreasing. Thus, HP feeding drastically inhibited hepatic VLDL secretion in obese and lean Zucker rats by an undefined mechanism that was apparently related neither to de novo fatty acid synthesis nor to changes in oleate partitioning between esterification and oxidation. Copyright (C) 1995 by W.B. Saunders Company