GSE196428
Quantitative analysis of Bckdhaf/f;RIP-Cre and Bckdhaf/f mice eWAT, iWAT and liver transcriptomes
To explore the underlying mechanism for the regulatory role of branched-chain amino acids (BCAA) catabolism in hypothalamic RIP-Cre neurons to metabolic organs under normal chow diet feeding, we established RIP-Cre neurons selective BCAA catabolic enzyme branched-chain ketoacid dehydrogenase E1 subunit alpha(Bckdha) knockout mice, we conducted RNA sequencing on the inguinal adipose tissue (iWAT), epididymal adipose tissues (eWAT), and liverfrom wild type (WT, Bckdhaf/f) and knockout (KO, Bckdhaf/f;RIP-Cre) mice  (two groups in total). Three biological replicates were performed for each group. Methods: RNA sequencing (RNA-Seq) and data analysis were performed by Gene Denovo Biotechnology (Guangzhou, China). Results: In comparison with findings in the Bckdhaf/f group, 393 up-regulated and 214 down-regulated differentially expressed genes (DEGs) were identified in eWAT from Bckdhaf/f;RIP-Cre group . Similarly, 41 up-regulated genes and 152 down-regulated DEGs were identified in iWAT from Bckdhaf/f;RIP-Cre compared to the Bckdhaf/f group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that DEGs in eWAT were enriched in the categories including all subclass pathways in carbohydrate metabolism class, insulin resistance, PPAR signaling, oxidative phosphorylation, thermogenesis, carbon metabolism, fatty acid metabolism, biosynthesis of amino acids and degenerative disease pathways. Similarly, DEGs in iWATwere clustered in the pathways, including the TCA cycle, pyruvate metabolism, glucagon signaling, glycolysis and gluconeogenesis, and carbon metabolism. These changes indicated broad disturbance in WAT energy metabolism in Bckdhaf/f;RIP-Cre mice. Liver transcriptomes showed minor perturbances in subclasses in lipid metabolism, advanced glycation end products and their receptor (AGE-RAGE), PPAR, estrogen, prolactin signaling pathways. Notably, all 13 mitochondrial DNA encoded mRNA were all significantly down-regulated in eWAT of Bckdhaf/f;RIP-Cre mice, along with nucleus DNA encoded mitochondrial located mRNA. Conclusions: Our results using RNA-Seq indicated universal defects of mitochondrial gene expression in eWAT and iWAT. Overall design: iWAT, eWAT, and liver mRNA profiles of 12-week old Bckdhaf/f;RIP-Cre and Bckdhaf/f mice