Effects of portacaval shunt on the genetically obese Zucker Rat.

Male adult obese (fa/fa) Zucker rats with high hypertriglyceridemia and hyperinsulinemia, and mild hypercholesterolemia were submitted to a portacaval shunt in order to examine the effects of this shunt on blood lipids and lipid synthesis. Sham-operated pair-fed obese (fa/fa) Zucker rats, obese (fa/fa) Zucker rats fed ad libitum, and lean (Fa/?) littermates fed ad libitum served as controls. In fa/fa rats 3 wk after portacaval shunt, fasting serum values of triacylglycerol (-70%) and cholesterol (-43%) were lower and plasma total glucagon was higher (+68%) than in pair-fed sham-operated fa/fa controls. In the same rats 4 wk after portacaval shunt and while fed ad libitum, serum protein was reduced by 22%, plasma pancreatic glucagon was 100% higher, and the hyperinsulinema was not modified. At that time, the wet weight of the liver and its total content in DNA, RNA, protein, and glycogen was decreased by 43%, 22%, 34%, 39%, and 60%, respectively. The in vivo incorporation of 3H2O into liver fatty acids was 76% lower and that into liver cholesterol eas 43% lower, per total organ, while the labeling of glyceride fatty acids was not modified in epididymal adipose tissue when compared with pair-fed fa/fa Zucker rats. In conclusion, portacaval shunting lowered blood triacylglycerol and cholesterol levels in fa/fa rats, and this was due, at least partially, to reduction in hepatic lipogenesis and cholesterologenesis.