The Role of Dietary Lipid in the Regulation of Unconjugated Hyperbilirubinaemia in Gunn Rats

Abstract

1. The purpose of this study was to characterize the mechanisms of diet-induced hyperbilirubinaemia in Gunn rats with emphasis on the role of lipids, and to examine their relationship with regard to fasting hyperbilirubinaemia. 2. A lipid-free normocaloric diet produced a threefold increase in plasma bilirubin concentration (baseline 109.4 mumol/l), which was maximal by 10 days and thereafter remained constant. The level of hyperbilirubinaemia attained was not influenced by fasting or phenobarbitone, and returned to baseline concentration within 10 days of resuming a normal diet. 3. Determination of hepatic bilirubin showed that the magnitude of the hepatic bilirubin pool was increased by the lipid-free diet but was unchanged by fasting. Hepatic ligandin concentrations were comparable in fasted Gunn rats and those fed normal or lipid-free diets, although total hepatic ligandin was reduced in the fasted animals. 4. The hyperbilirubinaemic effect of the lipid-free diet was largely reversed by the inclusion of 10% lipid in the diet and was affected to a lesser extent by 5% lipid. Similar reductions in plasma bilirubin concentration were observed with a variety of other lipids (10%), regardless of their fatty acid chain length or degree of saturation. 5. In fasting animals a direct correlation was observed between plasma bilirubin and free fatty acid concentrations and insulin levels were greatly depressed, whereas in those fed on the lipid-free diet no significant changes were evident in plasma concentrations of free fatty acids or insulin. 6. Plasma bilirubin concentration was unrelated to alterations in plasma triglycerides produced by the administration of clofibrate. However, an unexplained decrease in plasma bilirubin (40%) without a significant change in triglycerides was noted when clofibrate was added to the lipid-free diet. 7. Analysis of kinetic data obtained from [14C]bilirubin clearance studies revealed that hyperbilirubinaemia associated with the lipid-free diet reflected a marked reduction (60%) in plasma clearance with no change in bilirubin turnover. This was accompanied by a relative redistribution of bilirubin from the extravascular pool to the plasma pool. 8. Although these studies indicate that fasting and the withdrawal of dietary lipid have some similar effects on bilirubin metabolism, it seems likely that different mechanisms are responsible for the hyperbilirubinaemia.

Effects of Nutrition on Unconjugated Plasma Bilirubin Concentrations in Squirrel Monkeys†

“…Whitmer and Gollan (4) found that dietary fat must be reduced to an extremely low level (perhaps to 0.6% of the total caloric intake) to produced hyperbilirubinemia in Gilbert's subjects. Lipid-free diets caused unusually high plasma bilirubin concentrations in Gunn rats which are reduced by small lipid supplements (29). In contrast to those observations in humans and rats, fasting plasma bilirubin concentrations in Bolivian squirrel monkeys fed 5% fat (11% of calories) were lower than those fed very low-(0.3%) or high-fat (20%) diets.…”

Fasting Hyperbilirubinemia and Its Relationship to Free Fatty Acids and Triglycerides in the Horse

“…In the present study there is a high correlation between serum total bilirubin and free fatty acids in horses; this was further improved by the addition of triglycerides to the regression equation. An association between plasma triglycerides and bilirubin is not found in Gunn rats (25). However, plasma free fatty acid concentrations are related to the degree of fasting bilirubinemia in Gunn rats (26) and man (27).…”

“…Oral saline o r 400-kcal quantities of mannitol or amino acids do not affect serum bilirubin (31) or free fatty acid concentrations (32,33 . A recent study compared the effects of food deprivation and lipid withdrawal and suggested that these factors may influence bilirubinemia through different mechanisms (25). The mechanism of fasting bilirubinemia is obscure.…”

Effective oral treatment of unconjugated hyperbilirubinemia in Gunn rats†

“…30 The present data indicate that plasma UCB levels are almost twice as high in Gunn rats fed a LF diet compared with a HF diet. Gollan et al 45 showed that a fat-free diet increased plasma bilirubin concentrations threefold in Gunn rats. They reported that dietary supplementation with a variety of fats largely reversed the increased hyperbilirubinemia, regardless of their fatty acid chain length or degree of saturation.…”