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Quantitative analysis of Bckdhaf/f RIP-Cre and Bckdhaf/f mice eWAT, iWAT and liver transcriptomes

ABSTRACT: Quantitative analysis of Bckdhaf/f RIP-Cre and Bckdhaf/f mice eWAT, iWAT and liver transcriptomes

PROVIDER: PRJNA804885 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17957727_1.fastq.gz	Fastqsanger.gz
	SRR17957727_2.fastq.gz	Fastqsanger.gz
	SRR17957728_1.fastq.gz	Fastqsanger.gz
	SRR17957728_2.fastq.gz	Fastqsanger.gz
	SRR17957729_1.fastq.gz	Fastqsanger.gz

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Project description: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.

Project description:Objective: Procyanidins are polyphenolic bioactive compounds that exert beneficial effects against obesity and its related diseases. The aim of this study was to evaluate whether the supplementation with low doses of a grape seed procyanidin extract (GSPE) to dams during pre and postnatal periods has biological effects on their offspring at youth. Design: The metabolic imprinting effect of GSPE was evaluated in 30 days-old male offspring of four groups of rats that were fed either a standard diet (STD) or a high-fat diet (HFD) and supplemented with either GSPE at 25 mg per kg of body weight/day or vehicle during pregnancy and lactation. Results: A significant increase in the adiposity index and in the weight of all the white adipose tissue depots studied (retroperitoneal â??RWAT-, mesenteric â??MWAT-, epididymal â??EWAT- and inguinal â??IWAT-) was observed in offspring of dams fed with a HFD and treated with GSPE (HFT group), compared to the offspring of dams fed with the same diet and that do not received procyanidins (HF group). HFT animals also showed a higher number of cells in the EWAT, a sharply decrease of the circulating levels of monocyte chemoattractant protein-1 (MCP-1) as well as a moderate, but significant, decrease of plasma glycerol levels. The transcriptomic analysis performed in the EWAT showed 238 genes differentially expressed between HF and HFT animals, covering an entire range of processes related with the immune function and the inflammatory response (the metabolic pathway mainly reflected in the EWAT), adipose tissue remodeling and function, lipid and glucose homeostasis and metabolism of methyl groups. Conclusion: GSPE treatment to dams fed a HFD during pregnancy and lactation increases adiposity, decreases the circulating levels of MCP-1 and modulates the expression of key genes involved in the adipose tissue metabolism of their offspring. The microarray study was performed with the EWAT RNA samples of rats from the HF and the HFT groups (n=8 animals each).

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Quantitative analysis of Bckdhaf/f RIP-Cre and Bckdhaf/f mice eWAT, iWAT and liver transcriptomes

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