Fat Absorption and Metabolism in Bile Duct Ligated Rats

Abstract

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.

Effects of chronic metal exposure on wild fish populations revealed by high-throughput cDNA sequencing

“…In support of this hypothesis, it has been shown that Cd causes a rapid decrease in bile flow and complete cholestasis in isolated perfused rat livers (Soto et al 2002). Moreover, cholestasis, by reducing bile flow, triggers malabsorption of dietary retinoids (de Vriese et al 2001;Weiss et al 2010). Several studies in rats have shown that dietary retinol associated with chylomicrons is, under normal conditions, taken up by hepatocytes, metabolized into retinaldehyde and retinoic acid by cytosolic alcohol dehydrogenases, retinol dehydrogenases and several aldehyde dehydrogenases before being accumulated, mainly in hepatic stellate cells (Parés et al 2008).…”

“…Indeed, absorption of dietary lipids requires the presence of BAs. Reduction in bile flow during cholestasis or after bile duct ligation triggers malabsorption of dietary fatty acids (de Vriese et al 2001). Moreover, it is well established that dietary fatty acids regulate the transcription levels of various genes involved in energy metabolism by activating several families of ligand-activated transcription factors such as the peroxysome proliferator-activated receptor (PPAR; Desvergne and Gerald 2007;Jump et al 2005;Schoonjans et al 1995).…”

Human chorionic-plate-derived mesenchymal stem cells restore hepatic lipid metabolism in a rat model of bile duct ligation

“…De Vriese and colleagues reported the results of lipid analysis of BDL rats and identified hypercholesterolemia and changes in the serum phospholipid profile, in proportion to serum levels of total bilirubin and ALP; however, a decrease in liver fat content in BDL rats was also observed [4]. In a more recent study, a high-cholesterol diet was not found to cause hepatic steatosis in BDL mice [25].…”

“…Because bile acids play a key role in lipid and energy homeostasis, alterations in lipid metabolism are inevitable in cholestatic liver diseases [4,5,25]. De Vriese and colleagues reported the results of lipid analysis of BDL rats and identified hypercholesterolemia and changes in the serum phospholipid profile, in proportion to serum levels of total bilirubin and ALP; however, a decrease in liver fat content in BDL rats was also observed [4].…”

Water-soluble extract of Coleus barbatus modulates weight gain, energy utilization and lipid metabolism in secondary biliary cirrhosis: an experimental study in young rats

“…Ligature and common bile duct resection can be used as a model of the alterations of cholesterol metabolism in biliary atresia 28 . Cholestasis increased the serum levels of total cholesterol and triacylglycerides, which is in accordance with the literature 8 .…”