Addition of lipid to total parenteral nutrition prevents hepatic steatosis in rats by lowering the portal venous insulin/glucagon ratio.

Hepatic steatosis in rats is associated with an infusion of excessive carbohydrate calories. Previous work from this laboratory suggested that this is associated with an elevated portal insulin/glucagon molar ratio (I/G) and is reversed by parenteral glucagon administration. Although hepatic steatosis is not related to essential fatty acid deficiency, addition of lipid to total parenteral nutrition (TPN) has been reported as being protective against the development of hepatic steatosis. Therefore, we propose that lipid may exert its salutary effect via an alteration of the I/G ratio. To test this hypothesis, adult rats (seven per group) received internal jugular catheters: group 1, saline (3 mL/h) plus chow ad libitum; group 2, 25% dextrose base TPN; group 3, 17% dextrose base TPN + 2.5% lipid; group 4, 25% dextrose base TPN + 2.5% lipid. At 7 days, portal and peripheral venous blood was drawn for insulin and glucagon radioimmunoassay and liver function tests; livers were removed for histology and lipid content determination. Panlobular vacuolization, on histology, and lipid content were excessive in group 2, and the portal I/G was increased because of elevated portal insulin. In contrast, portal venous insulin and I/G did not increase, and hepatic steatosis was absent in groups 3 and 4. The results suggest that the addition of lipid to TPN in rats decreases the portal insulin level and lowers the portal I/G, and thereby prevents hepatic steatosis.