Fat absorption and metabolism in bile duct ligated rats

Background. Bile excretion is obstructed in children with extrahepatic bile duct atresia (EHBA) resulting in fat malabsorption and disturbed lipid met abolism. Aim: Investigate if the bile duct ligated rat exhibits similar dev iations as patients with EHBA under different feeding conditions. Methods: 6 bile duct ligated Wistar rats and 12 matched paired controls were randomi sed over 3 feeding groups. Rats were killed 16 or 30 days postsurgery. Faec es, blood and livers were collected. Fat absorption was evaluated, markers for cholestasis and the fatty acid composition of serum phospholipids (PL) and cholesterol esters (CE) were determined. Fatty acid desaturation activi ties in liver microsomes were measured. Results: Cholestatic bile duct liga ted rats have a lower fat absorption coefficient and a lower fraction of 18 :2n-6 and 18:3n-3 in serum triglycerides than their controls. This demonstr ates that bile duct ligated rats suffer from fat malabsorption. In contrast to the observations in serum triglycerides, 18:2n-6 and 18:3n-3 were not r educed in serum PL and CE of cholestatic rats. Overflow of 18:2n-6 rich bil iary PL in the general circulation could contribute to this observation. In agreement with what was found in man, serum PL of cholestatic rats have a higher 16:0/18:0 ratio, increased monoenes and reduced unsaturated fatty ac ids. However, no differences were observed in microsomal desaturation activ ities. Conclusion: Cholestatic bile duct ligated rats exhibit similar devia tions in serum fatty acid composition as found in patients with EHBA, there fore they can be used as a model for this human disease.