RNA-Seq analysis of obese <i>Pdha1^fl/fl</i>Lyz2-Cre mice induced by a high-fat diet

Abstract

Pyruvate dehydrogenase complex (PDH) is an important complex of three enzymes that transforms pyruvate into acetyl-CoA, subsequently entering the tricarboxylic acid (TCA) cycle to produce ATP and electron donors. As a key regulator of energy and metabolic homeostasis, PDH is considered a potential therapeutic target of many diseases. On the other hand, the relationship between PDH and obesity is not clear. In this study, peripheral blood of Pdha1 fl/fl Lyz2-Cre and C57BL/6 mice fed a high-fat diet (HFD) was collected and subjected to extensive transcriptome sequencing.Differentially expressed genes (DEGs) were identified. Enrichment of functions and signaling pathways analyses were performed based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the genes selected from RNA sequencing (RNA-seq). Eventually, we found that Pdha1 fl/fl Lyz2-Cre mice were more susceptible to HFD-induced obesity. A total of 302 up-regulated genes and 30 downregulated genes were screened that were differentially expressed between Pdha1 fl/fl Lyz2-Cre mice fed the HFD and the control groups. Furthermore, we verified that significant transcriptional changes in the genes Sgstm1,