It has been reported that hyperlipidemia can be alleviated in human beings with an end to side portacaval shunt. Understanding the mechanism of the effect has important implications, including the possibility of devising other ways of lowering serum lipid levels. In this investigation, the influence of splanchnic venous blood on lipid metabolism was evaluated in dogs and baboons by altering the portal venous inflow to all, or portions, of the liver and by measuring the effects on different end points, including the serum lipid concentrations and the rate of hepatic lipid synthesis. In other studies, analyses have been made regarding the effect of alloxan induced insulinopenia and of total pancreatectomy on these processes. The results indicate that the effect of complete portal diversion upon serum lipids is mainly due to diversion of the hormone rich venous return from the upper splanchnic organs, although the bypass of the nutritionally rich blood returning from the intestines may play a secondary role. Therefore, a reduction of hepatic lipid synthesis is an important, although not necessarily the sole, factor in the antilipidemic influence of portacaval shunt. The effects upon synthesis and blood lipids are due more to the diversion of endogenous hormones than to the bypass of intestinal nutrients. The substances in portal venous blood that subserve hepatic lipid metabolism are presumably largely the same as the hepatotrophic factors which have been described before as profoundly affecting hepatic structure, function, and the capacity for regeneration. These portal blood factors are multiple and interrelated, but the single most important one seems to be insulin
