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Fat absorption and metabolism in bile duct ligated rats
S R De Vriese1, J L Savelii, J P Poisson
1Department of Endocrinology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. Stephanie.DeVriese@rug.ac.be
Insights
Bile duct ligation in rats causes fat malabsorption and altered serum fatty acids, mimicking human extrahepatic bile duct atresia (EHBA). These rats serve as a valuable model for studying EHBA lipid metabolism.
Area of Science:
- Biochemistry
- Physiology
- Animal Models
Background:
- Extrahepatic bile duct atresia (EHBA) in children obstructs bile flow, leading to fat malabsorption and altered lipid metabolism.
- Understanding these metabolic disturbances is crucial for developing effective treatments.
Purpose of the Study:
- To investigate if bile duct ligated rats replicate the lipid metabolism deviations observed in human EHBA patients.
- To assess the impact of different feeding conditions on these deviations.
Main Methods:
- Bile duct ligation was performed on Wistar rats, with controls randomized into three feeding groups.
- Rats were analyzed 16 or 30 days post-surgery, examining feces, blood, and liver tissues.
- Fat absorption, cholestasis markers, serum phospholipid (PL) and cholesterol ester (CE) fatty acid composition, and liver microsomal desaturation activities were measured.
Main Results:
- Bile duct ligated rats showed reduced fat absorption and lower levels of linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3) in serum triglycerides, confirming fat malabsorption.
- Serum PL and CE fatty acid profiles in cholestatic rats mirrored those in EHBA patients, with a higher palmitic to stearic acid (16:0/18:0) ratio and reduced unsaturated fatty acids.
- No significant differences in microsomal fatty acid desaturation activities were observed between groups.
Conclusions:
- Cholestatic bile duct ligated rats exhibit similar serum fatty acid composition changes as seen in human EHBA.
- These rats represent a suitable animal model for studying extrahepatic bile duct atresia and its associated lipid metabolism disorders.
Background:
Bile excretion is obstructed in children with extrahepatic bile duct atresia (EHBA) resulting in fat malabsorption and disturbed lipid metabolism.
Aim:
Investigate if the bile duct ligated rat exhibits similar deviations as patients with EHBA under different feeding conditions.
Methods:
6 bile duct ligated Wistar rats and 12 matched paired controls were randomised over 3 feeding groups. Rats were killed 16 or 30 days postsurgery. Faeces, 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 activities in liver microsomes were measured.
Results:
Cholestatic bile duct ligated 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 demonstrates 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 reduced in serum PL and CE of cholestatic rats. Overflow of 18:2n-6 rich biliary 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 acids. However, no differences were observed in microsomal desaturation activities.
Conclusion:
Cholestatic bile duct ligated rats exhibit similar deviations in serum fatty acid composition as found in patients with EHBA, therefore they can be used as a model for this human disease.