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Aiming the search of novel regulators of lipid metabolism and their potential targets, in this study we performed molecular modeling of eight isomeric 17(20)Z- and 17(20)E-pregna-5,17(20)-dien-21-oyl amides differing in structure of the amide moiety. Analysis of the low energy conformers revealed that all 17(20)E-isomers had three main energy minima (corresponding to values of the dihedral angle theta20,21 (C17 = C20-C21 = 0) to approximately 0 degrees, to approximately 120 degrees and to approximately 240 degrees), the most occupied minimum was found to correspond to theta20,21 to approximately 0 degrees; while 17(20)Z-isomers had either one or two pools of low energy conformations. Molecular docking of these compounds to the ligand-binding site of the nuclear receptor LXRbeta (a potential target) indicates high probability of binding for E-isomers and the absence of that for Z-isomers. Results of the molecular modeling were confirmed by an experiment in which stimulation of triglyceride biosynthesis in Hep G2 cells in the presence of 17(20)E-3beta-hydroxypregna-5,17(20)-dien-21-oyl (hydroxyethyl)amide was demonstrated.

As a signaling molecule with system endocrine function, UDCA improves insulin sensitivity by activating the nuclear farnezoid X-receptor; as a ligand for the TGR5/Gpbar-1 receptor, UDCA is able to stimulate the secretion of GLP-1. UDCA ameliorate of the anti-oxidative defenses in NAFLD, normalizes NAD+/NADH ratio, beta-oxidation. UDCA improves the liver biochemical and histological picture in NASH, also reduces hepatocytes apoptosis and restores adiponectin levels; in other studies, these data are not confirmed. In the experiment, UDCA prevents the development of steatosis in the liver. UDCA may increase efficiency in combination with statins, thiazolidinediones, vitamin E. Further controlled prospective trials are needed for research of the UDCA effect in NAFLD.