Full Transcriptome Profiling of the Liver of Fat-, Fructose- and Cholesterol-Fed C57Black/6J Mice

Abstract

C57black/6J female mice were fed an isocaloric diet with excess fat, fructose, cholesterol, or combinations of them for 62 days. In their liver, the differential expression of 30 003 genes was studied by full-chip transcriptional profiling on an Agilent One-Color Microarray-Based Gene Expression Analysis Low Input Quick Amp Labeling, version 6.8, and the relative levels of mRNA for the genes Gpr19, P2ry12, Gnb1, Csf2rb, Gm38450, Pgm3, Prom2, and Adgrv1 were also evaluated by real-time RT-PCR. To determine the metabolic pathways (KEGG), which are the targets of the applied dietary influences, we analyzed the transcriptome data by bioinformatics methods in the R programming environment. We revealed a specific effect of experimental diets on the metabolic pathways of JAK-STAT and MAPK kinases, VEGF and TOR signaling pathways, and a family of transcription factors PPAR. It reflects the changes occurring in the liver in intracellular signaling, inflammation and angiogenesis. The consequences of such changes may be the development of insulin resistance and fatty hepatosis. For the first time, we revealed experimentally a specific effect of all kinds of diets on metabolic pathways of amino acid metabolism of aspartate, glutamate, alanine, proline, histidine, and arginine. Using real-time RT-PCR, we analyzed the samples derived from the groups of animals that received excess fat with fructose or cholesterol. We detected the coordinated changes in expression levels of the Gpr19, Adgrv1, and Csf2rb genes, reflecting the integrated shifts in the cytokine production profiles and the neurohormonal regulation of metabolic processes.