Abstract: Differential expression of 30 584 genes from a microarray was studied in the liver of male Wistar rats, fed for 63 days with high-fat high-fructose diet supplemented with L-carnitine, resveratrol, tyrosine, or tryptophan, using the method of whole-transcriptome gene expression profiling according to the Agilent One-Color Microarray-Based Gene Expression Analysis Low Input Quick Amp Labeling protocol (version 6.8). To identify metabolic pathways (KEGGS) that are the targets of the applied dietary treatments, transcriptomic data were processed with bioinformatics methods in the R environment. The data obtained suggest that the intake of biologically active substances, i.e., lipid metabolism modulators (including L-Car, Res, and Tyr and Trp aromatic amino acids), despite clear differences in primary targets of their effects and phenotypic consequences for the organism at tissue and organ levels, at the intermediate stages engages a complex of genes that are largely similar and interrelated in their function. These genes are involved in the regulation of cell cycle, proliferation, apoptosis, intercellular interactions, immune response, and inflammation. Moreover, the sign of DE of each of these genes, taken separately, does not allow for unambiguous prediction the direction of processes manifested in strengthening or, alternatively, attenuation of lipogenesis and the observed accumulation of fatty inclusions in the liver cells. Newly described, not reported in the available literature, is the differentiated effect between L-Car, Res, and Tyr, on one hand, and Trp, on the other hand, on the metabolic pathway of arachidonic acid, including the formation of oxylipins (lipoxins), prostaglandins, and thromboxanes.