Transcriptome analysis of propionic acid regulating gluconeogenesis of bovine hepatocytes

Propionate is the primary precursor of glyconeogenesis in bovine hepatocytes; however, the regulatory mechanism involved is still unclear. The aim of this study was to investigate the effects of propionate on gluconeogenesis in bovine hepatocytes and the underlying regulatory molecular mechanisms. Bovine hepatocytes were treated with 3.75 mmol·L⁻¹ propionate, and cells were collected for transcriptome sequencing. Differentially expressed genes (DEGs) were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The results showed that the glucose content increased after propionate addition, compared to its content in the control group (P < 0.05). A total of 331 DEGs (false-discovery rate < 0.05) were identified using RNA sequencing (222 up-regulated genes and 109 down-regulated genes). The expression levels of 10 randomly selected DEGs, determined using qRT-PCR, were consistent with the RNA sequencing analysis results. Propionate addition reduced the expression levels of oxidation-related genes (GPX2 and GPX7), while increasing the expression levels of inflammation-related genes of bovine hepatocytes (CYP1A1, CYP1B1, and ARRB1). According to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes functional analyses, the functions of these DEGs were classified into 115 GO items that were mainly concentrated on catalytic activity and binding. Twelve metabolic pathways were significantly (P < 0.05) enriched, and the DEGs were mainly enriched in insulin secretion and MAPK signaling pathways. This study identified relevant genes and pathways involved in the regulation of gluconeogenesis in bovine hepatocytes by propionic acid. This will provide new ideas for targeting the efficient utilization of low-quality forage by lactating dairy cows.