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
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