Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats.
Hepatic steatosis is one of the two principal hepatic complications of total parenteral nutrition (TPN), the other being cholestasis. While the cause is uncertain, an excess of carbohydrate calories in rats leads to an elevated portal insulin/glucagon (I/G) molar ratio, periportal fatty infiltration, and increased total hepatic lipid content. Insulin causes fatty acid biosynthesis, whereas glucagon causes hepatic release and inhibition of fatty acid synthesis. Thus we attempted to add glucagon to lower the I/G to see if this would affect the degree of hepatic fatty infiltration by encouraging hepatic fat mobilization. Adult rats (n = 21) received internal jugular catheters; Group 1 (n = 7) was given saline solution (3 ml/h) and chow ad libitum; Group 2 (n = 7), 25% dextrose-base (D25W) TPN solution; Group 3 (n = 7), D25W TPN + 33 micrograms/100 gm/day glucagon. At 7 days portal and peripheral venous blood samples were drawn for insulin and glucagon radioimmunoassay and blood glucose determination; livers were removed for histologic study and lipid determination. Blood glucose did not differ in any group. Hepatic lipid and peripheral and portal venous I/G were increased and periportal fatty infiltration was extensive in Group 2, whereas hepatic lipid and I/G were decreased and periportal fatty infiltration was absent in glucagon-infused rats (Group 3). An abnormally high I/G ratio in portal blood elicited by high-glucose TPN may be responsible, at least in part, for hepatic steatosis. By increasing hepatic lipid export, addition of glucagon to TPN may play a major role in decreasing hepatic steatosis.
D000818:Animals; D005227:Fatty Acids / Q000096:biosynthesis*; D005234:Fatty Liver / Q000209:etiology / Q000517:prevention & control*; D005934:Glucagon / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008053:Lipid Mobilization; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D051381:Rats; D011919:Rats, Inbred Strains
D005227:Fatty Acids; D007328:Insulin; D005934:Glucagon