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ABSTRACT: Hormonally Induced Hepatocellular Carcinoma in Diabetic Wild Type and Carbohydrate Responsive Element Binding Knockout Mice

PROVIDER: PRJNA772721 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16492467_1.fastq.gz	Fastqsanger.gz
	SRR16492467_2.fastq.gz	Fastqsanger.gz
	SRR16492468_1.fastq.gz	Fastqsanger.gz
	SRR16492468_2.fastq.gz	Fastqsanger.gz
	SRR16492469_1.fastq.gz	Fastqsanger.gz

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Project description:Glycerol kinase (GK) is at the interface of fat and carbohydrate metabolism and has been implicated in insulin resistance and type 2 diabetes mellitus (T2DM). To define GK’s role in insulin resistance, we examined gene expression in brown adipose tissue in a glycerol kinase (Gyk) knockout (KO) mouse model using microarray analysis. Global gene expression profiles of KO mice were distinct from wild type (WT) with 668 genes that were differentially expressed. These included genes involved in lipid metabolism, carbohydrate metabolism, insulin signaling, and insulin resistance. Real-Time (RT) PCR analysis confirmed the differential expression of selected genes involved in lipid and carbohydrate metabolism. PathwayAssist analysis confirmed direct and indirect connections between GK and genes in lipid metabolism, carbohydrate metabolism, insulin signaling, and insulin resistance. Network Component Analysis (NCA) showed that the transcription factors, peroxisome proliferator-activated receptor gamma (PPAR-γ), sterol regulatory element binding factor 1 (SREBP-1), SREBP-2, signal transducer and activator of transcription 3 (STAT3), STAT5, trans-acting transcription factor 1 (SP1), CCAAT/enhancer binding protein alpha (CEBP-α), cAMP responsive element binding protein 1 (CREB), glucocorticoid receptor (GR), and PPAR-α have altered activity in the KO mice. NCA also revealed the individual contribution of these transcription factors on the expression of genes altered in the microarray data. This study elucidates the transcription network of Gyk and further confirms a role for Gyk, a simple Mendelian disorder, in insulin resistance and T2DM, a common complex genetic disorder. Keywords: genotype state analysis

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