Effect of a Farnesoid X-receptor Agonist on Postprandial Lipemia in Rats Fed a Supraphysiological Fat Dozes

Abstract

Introduction. One of the most progressive directions of the modern stage of development of biology is the deepening of knowledge about the mechanisms of regulation of metabolic processes, in particular about signal molecules that transmit information to the cell through ion channels and nuclear receptors associated with G-protein or with enzymatic activity. The nuclear Farnesoid X receptor (FXR) is mainly expressed in the liver and intestines, it regulates key genes that provide the processes of synthesis, transport and reabsorption of bile acids, and is also involved in the metabolism of lipids and carbohydrates.Aim. To evaluate the effect of a farnesoid X receptor agonist on postprandial lipemia in rats fed a supraphysiological fat diet.Materials and methods. An experimental, prospective, controlled, unblinded, randomized study was conducted to study the effect of a farnesoid X receptor agonist (obeticholic acid) on postprandial lipemia in rats receiving a diet containing a supraphysiological dose of fats.Results and discussion. It has been shown that when assessing postprandial lipemia, an oral test for tolerance to supraphysiological doses of fat with the determination of the initial lipid profile parameters and 4 hours after exercise has a sufficiently high information content. It was found that in animals that received a diet containing an increased amount of fat for 28 days, there was an imbalance in lipid metabolism with activation of their absorption in the intestine, but a "slow" reaction of the mechanisms of intermediate lipid metabolism, which was accompanied by the accumulation of triglycerides and cholesterol in the blood of hungry rats, chylomicrons and LDL. At 4 hours post-feeding, these animals showed abnormal increases in triglycerides and cholesterol.Conclusion. The use of obeticholic acid harmonizes lipid metabolism against the background of alimentary fat load, due to the activation of farnesoid X-receptors of the intestine and liver, which is manifested by a simultaneous increase in the intensity of lipid absorption processes and their intermediate metabolism. As a result, the risk of hyperchylomicronemia, hypercholesterolemia and hypertriglyceridemia is eliminated, the likelihood of developing secondary hyperlipedemia, insulin tolerance and functional overload (or pathology) of the liver is reduced.

Peculiarities of clinical and laboratory manifestations of hepatopathy: The path to medical consensus

“…The value of bile acids as a way to diagnose liver pathologies lies in their specificity and uniqueness. It is also worth noting their potential for use in monitoring the therapy of liver diseases [17][18][19][20][21][22][23][24].…”

“…From the data presented above, it is clear that hepatopathy in all animal species manifests itself as pathological syndromes of the same type. Cytolysis syndrome, which occurs as a result of the destruction of hepatocyte membranes and the release of cell contents into the intercellular space, manifests itself biochemically as an increase in the enzymes contained in the cytoplasm and mitochondria of liver cells (AST, ALT, and LDH) and an increase in the concentration of bilirubin (urobilinuria) [17][18][19][20][21][22][23][24]. Cholestasis syndrome, which occurs due to disorders in the biliary system of the liver, manifests itself in the form of increased alkaline phosphatase and an increase in bilirubin in the blood.…”

The prevalence of hepatopathy in productive animals and aquaculture objects

“…When the liver is damaged, profound disturbances occur in the body's homeostasis. Due to the intensification of animal husbandry, animal owners often neglect sanitary and hygienic standards for feeding, care and use of productive animals [4][5]. As a result, the animals' adaptability to negative environmental factors decreases, and the liver experiences severe stress.…”