The Association between Fasting Hyperbilirubinaemia and Serum Non-Esterified Fatty Acids in Man

Cowan, Robert Ernest; Thompson, R. P. H.; Kaye, Josse; Clark, Gillian M.

doi:10.1042/cs0530155

Cited by 7 publications

(8 citation statements)

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“…However, in contrast to the findings in both fasting human subjects (Cowan, Thompson, Kaye & Clark, 1977) and Gunn rats, the rise in plasma bilirubin concentration did not correlate with the plasma free fatty acids. Since an inverse relationship exists between plasma insulin concentrations and lipolysis, and the plasma insulin concentrations were unaltered by the lipid-free diet, it is unlikely that lipolysis plays a role in the dietary regulation of bilirubin metabolism.…”

Section: Discussioncontrasting

confidence: 99%

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

1979

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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.

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Section: Discussioncontrasting

confidence: 99%

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

1979

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“…Interference by FFA with bilirubin metabolism might occur at any stage from the transport of bilirubin in the blood to its conjugation by the liver cell (Cowan et al, 1977;Odi&vre, 1975) and, although there are alternative explanations for the transient unconjugated hyperbilirubinaemia after myocardial infarction, the relationship between concentrations of bilirubin and FFA found in this study supports the suggestion that bilirubin concentrations in the blood are influenced by the metabolism of FFA in the liver.…”

Section: Discussionsupporting

confidence: 81%

“…However, it was probably exceptional for the daily intake of these patients to be as low as 167 kJ and bilirubin concentrations fell gradually and not sharply when normal food intake was restored. The concentrations of serum FFA are increased after myocardial infarction, and they might elevate bilirubin concentrations by competitive interference with hepatic bilirubin clearance, a mechanism already proposed to explain the unconjugated hyperbilirubinaemia of fasting (Cowan et al, 1977). Bilirubin and FFA concentrations did not change synchronously in this study but bilirubin concentrations will be slower than FFA to respond to changes in the rate of hepatic uptake, so plasma bilirubin will not change in parallel with the faster changes of serum FFA.…”

Section: Discussionmentioning

confidence: 44%

Plasma bilirubin and serum free fatty acids after myocardial infarction

Cowan¹,

Thompson²,

Kaye³

et al. 1981

Postgraduate Medical Journal

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SummaryFasting concentrations of plasma bilirubin were measured in 34 patients on admission to hospital and daily for 7 days after uncomplicated myocardial infarction. Mean concentrations increased significantly to reach maximum levels on the second day after admission, and fell during the following 5 days to reach the admission level by the 7th day. Unconjugated bilirubin accounted for most of this rise. Serum concentrations of free fatty acids (FFA), measured simultaneously in 12 patients, were highest within 12 hr of the onset of symptoms, when their level was significantly higher than at any time after the first day. It is suggested that the transient hyperbilirubinaemia after uncomplicated myocardial infarction is frequent and may result from interference by FFA with bilirubin metabolism.

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“…On the other hand, serum bilirubin concentrations can influence free fatty acid metabolism [44]. Furthermore, free fatty acids may interfere with bilirubin metabolism at any stage, from blood transport to its conjugation by the hepatocyte [45], [46], and the control of serum bilirubin concentrations may be linked to lipid metabolism [45].…”

Section: Discussionmentioning

confidence: 99%

A Cohort Study of Serum Bilirubin Levels and Incident Non-Alcoholic Fatty Liver Disease in Middle Aged Korean Workers

et al. 2012

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BackgroundSerum bilirubin may have potent antioxidant and cytoprotective effects. Serum bilirubin levels are inversely associated with several cardiovascular and metabolic endpoints, but their association with nonalcoholic fatty liver disease (NAFLD) has not been investigated except for a single cross-sectional study in a pediatric population. We assessed the prospective association between serum bilirubin concentrations (total, direct, and indirect) and the risk for NAFLD.Methods and FindingsWe performed a cohort study in 5,900 Korean men, 30 to 59 years of age, with no evidence of liver disease and no major risk factors for liver disease at baseline. Study participants were followed in annual or biennial health examinations between 2002 and 2009. The presence of fatty liver was determined at each visit by ultrasonography. We observed 1,938 incident cases of NAFLD during 28,101.8 person-years of follow-up. Increasing levels of serum direct bilirubin were progressively associated with a decreasing incidence of NAFLD. In age-adjusted models, the hazard ratio for NAFLD comparing the highest to the lowest quartile of serum direct bilirubin levels was 0.61 (95% CI 0.54–0.68). The association persisted after adjusting for multiple metabolic parameters (hazard ratio comparing the highest to the lowest quartile 0.86, 95% CI 0.76–0.98; P trend = 0.039). Neither serum total nor indirect bilirubin levels were significantly associated with the incidence of NAFLD.ConclusionsIn this large prospective study, higher serum direct bilirubin levels were significantly associated with a lower risk of developing NAFLD, even adjusting for a variety of metabolic parameters. Further research is needed to elucidate the mechanisms underlying this association and to establish the role of serum direct bilirubin as a marker for NAFLD risk.

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The Association between Fasting Hyperbilirubinaemia and Serum Non-Esterified Fatty Acids in Man

Cited by 7 publications

References 0 publications

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

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

Plasma bilirubin and serum free fatty acids after myocardial infarction

A Cohort Study of Serum Bilirubin Levels and Incident Non-Alcoholic Fatty Liver Disease in Middle Aged Korean Workers

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