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ECPB 2017, 79(3): 17–21
Research articles

Influence of L-cysteine on Lipid Composition of Bile in Rats


The liver is a polyfunctional organ that plays a crucial role in various types of metabolic processes, including lipid metabolism. Increased production and/or decreased clearance of lipid in the liver inevitably results in hypertriglyceridemia, while their accumulation in the liver can lead to nonalcoholic fatty liver disease. Recent studies have shown that L-cysteine plays a generalized role in the regulation of lipid profile in serum and tissues. It is known that L-cysteine reduces total lipoprotein lipase activity and activities of the lipogenic enzymes, increases catabolism of lipids and subsequent excretion of metabolic by-products through the intestinal tract. However, the specific role of L-cysteine in bile lipids formation and secretion, and especially the molecular mechanism by which this amino acid acts, continues to be unknown. The aim of our research is to find out the dynamic of changes in concentrations of bile lipids under conditions of a single bolus administration of L-cysteine.

All animal procedures have been approved by the Ethics Commission. The effect of L-cysteine (20 mg/kg) on bile lipid concentrations has been investigated in white laboratory outbred male rats weighing 250-300 g (n = 14), which have been kept in standard conditions in accredited vivarium. All animals have been anesthetized with an intraperitoneal injection of sodium thiopental (70 mg/kg) and operated to collect six samples of bile during 3 hours. After collection of the first sample animals have been treated by intraportal injection of L-cysteine at a dose of 20 mg/kg body weight. The rats in the control group have received physiological saline. Five bile lipid fractions have been measured using the method of thin-layer chromatography: free cholesterol, phospholipids, сholesterol esters, fatty acids and triglycerides. The concentration of each lipid fraction in the solution has been calculated against the calibration curve of the standard solution.

Our results indicate that administration of L-cysteine at a dose of 20 mg/kg body weight has decreased levels of all bile lipid fractions, especially free cholesterol level. Concentration of bile free cholesterol has reduced by 33.9 %, phospholipids decreased by 12.5 %, сholesterol esters – by 21.2 %, fatty acids and triglycerides – by 12.3 % and 18.5 % (р < 0.05) relative to baseline. Considering the data presented in this study, we suggest that effects of the investigated amino acid have been related to the regulatory activity of its metabolites. One mechanism by which L-cysteine may act is through its enzymatic breakdown to produce hydrogen sulphide (H2S), a gasotransmitter that regulates oxygen-dependent processes such as cholesterol synthesis. Also H2S can effect on ABCA1-mediated cholesterol efflux and cholesterol levels. That is why reduction of bile free cholesterol level could be related to up-regulation of ATP-binding cassette transporter A1 (ABCA1) and associated with it high-density lipoprotein formation or inhibiting of cholesterol synthesis. Another endogenic metabolite of L-cysteine is taurine, which reduces cellular free cholesterol level and enhance CYP7A1 expression to promote cholesterol conversion to bile acids. Thus, L-cysteine has decreased bile free cholesterol acting through taurine-mediated enhancement of lipid catabolism or H2S-mediated intensification of transport or inhibition of synthetic processes in hepatocytes.

Article recieved: 25.08.2017

Keywords: L-cysteine, bile, liver, hydrogen sulphide

Full text: PDF (Ukr) 875K

  1. 1. A.c. 4411066/14 USSR, MBІ G 01 N 33/50. A method of determining bile acids in biological fluids. Veselsky S, Liashenko P, Lykianenko I. (USSR). – № 1624322; stat. 25.01.88; publ. 30.01.91, Bull. № 4.
  2. 2. Attie AD. ABCA1: at the nexus of cholesterol, HDL and atherosclerosis. Trends Biochem Sci. 2007;32(4):172-9.
  3. 3. Boyer J. Bile Formation and Secretion. Comprehensive Physiology. 2013;3(3):1035-1078.
  4. 4. Burns M, Self K. Effects of cystine, niacin and taurine on cholesterol and bile acid metabolism in rabbits. Clinical and experimental metabolism. 1969;18(5):427-432.
  5. 5. Carey A, Zhang W, Setchell K, Simmons J, Shi T, Lages C et al. Hepatic MDR3 expression impacts lipid homeostasis and susceptibility to inflammatory bile duct obstruction in neonates. Pediatr Res. 2017;10:1038-47.
  6. 6. Carter R, Morton N. Cysteine and hydrogen sulphide in the regulation of metabolism: insights from genetics and pharmacology. Journal of Pathology. 2016;238:321-332.
  7. 7. Gong D, Cheng H, Xie W, Zhang M, Liu D, Lan G et al. Cystathionine γ-lyase(CSE)/hydrogen sulfide system is regulated by miR-216a and influences cholesterol efflux in macrophages via the PI3K/AKT/ABCA1 pathway. Biochem Biophys Res Commun. 2016;470(1):107-16.
  8. 8. Guo J, Gao Y, Cao X, Zhang J, Chen W. Cholesterol-lowing effect of taurine in HepG2 cell. Lipids Health Dis. 2017;16(1):56-67.
  9. 9. Jurkowska H, Stipanuk M, Hirschberger L, Roman H. Propargylglycine inhibits hypotaurine/taurine synthesis and elevates cystathionine and homocysteine concentrations in primary mouse hepatocytes. Amino. Acids. 2015;47(6):1215-23.
  10. 10. Kumari K, Augusti K. Lipid lowering effect of S-methyl cysteine sulfoxide from Allium cepa Linn in high cholesterol diet fed rats. J Ethnopharmacol. 2007;109(3):367-71.
  11. 11. Li D, Xiong Q, Peng J, Hu B, Li W, Zhu Y et al. Hydrogen Sulfide Up-Regulates the Expression of ATP-Binding Cassette Transporter A1 via Promoting Nuclear Translocation of PPARα. Int J Mol Sci. 2016;17(5):635-47.
  12. 12. Li Y, Wang X, Shen Z. Traditional Chinese medicine for lipid metabolism disorders. Am J Transl Res. 2017;9(5):2038-2049.
  13. 13. Norris E, Culberson C, Narasimhan S, Clemens M. The liver as a central regulator of hydrogen sulfide. Shock. 2011;36(3):242-50.
  14. 14. Oram J, Vaughan A. ATP-Binding cassette cholesterol transporters and cardiovascular disease. Circ Res. 2006;99(10):1031-43.
  15. 15. Peh M, Anwar A, Ng D, Atan M, Kumar S, Moore P. Effect of feeding a high fat diet on hydrogen sulfide (H2S) metabolism in the mouse. Nitric Oxide. 2014;41:138-145.
  16. 16. Tyazhka O, Smishchuk V, Bryuzgina T. Importance of bile biochemical studies as an indicator of fatty acids, phospholipids and cholesterol metabolic disorders in children with cholelithiasis. Perinatologiya and pediatriya. 2015;1(61):63-67.
  17. 17. Vaz F, Ferdinandusse S. Bile acid analysis in human disorders of bile acid biosynthesis. Mol Aspects Med. 2017;22(17):300-316.
  18. 18. Vedhachalam C, Duong Ph, Nickel M, Nguyen D, Dhanasekaran P, Saito H et al. Mechanism of ATP-binding Cassette Transporter A1-mediated Cellular Lipid Efflux to Apolipoprotein A-I and Formation of High Density Lipoprotein Particles. The Journal of Biological Chemistry. 2007;282:25123-25130.
  19. 19. Wu D, Zheng N, Qi K, Cheng H, Sun Z, Gao B et al. Exogenous hydrogen sulfide mitigates the fatty liver in obese mice through improving lipid metabolism and antioxidant potential. Med Gas Res. 2015;5(1):1-14.
  20. 20. Xu Z, Fan J, Ding X, Qiao L, Wang G. Characterization of high-fat, diet-induced, non-alcoholic steatohepatitis with fibrosis in rats. Dig Dis Sci. 2010;55:931-940.
  21. 21. Zhang L, Pan C, Yang B, Xiao Y, Yu B. Enhanced expression of cystathionine β-synthase and cystathionine γ-lyase during acute cholecystitis-induced gallbladder inflammation. PLoS One. 2013;8(12):10-25.

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