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Open AccessArticle

Cardiac Transcriptome Analysis Reveals Nr4a1 Mediated Glucose Metabolism Dysregulation in Response to High-Fat Diet

Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China
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Author to whom correspondence should be addressed.
Genes 2020, 11(7), 720; https://doi.org/10.3390/genes11070720
Received: 28 April 2020 / Revised: 19 June 2020 / Accepted: 23 June 2020 / Published: 29 June 2020
(This article belongs to the Special Issue Functional Genomics in Metabolic Diseases)
Obesity is associated with an increased risk of developing cardiovascular disease (CVD), with limited alterations in cardiac genomic characteristics known. Cardiac transcriptome analysis was conducted to profile gene signatures in high-fat diet (HFD)-induced obese mice. A total of 184 differentially expressed genes (DEGs) were identified between groups. Based on the gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs, the critical role of closely interlocked glucose metabolism was determined in HFD-induced cardiac remodeling DEGs, including Nr4a1, Fgf21, Slc2a3, Pck1, Gck, Hmgcs2, and Bpgm. Subsequently, the expression levels of these DEGs were evaluated in both the myocardium and palmitic acid (PA)-stimulated H9c2 cardiomyocytes using qPCR. Nr4a1 was highlighted according to its overexpression resulting from the HFD. Additionally, inhibition of Nr4a1 by siRNA reversed the PA-induced altered expression of glucose metabolism-related DEGs and hexokinase 2 (HK2), the rate-limiting enzyme in glycolysis, thus indicating that Nr4a1 could modulate glucose metabolism homeostasis by regulating the expression of key enzymes in glycolysis, which may subsequently influence cardiac function in obesity. Overall, we provide a comprehensive understanding of the myocardium transcript molecular framework influenced by HFD and propose Nr4a1 as a key glucose metabolism target in obesity-induced CVD. View Full-Text
Keywords: cardiac transcriptome analysis; high-fat diet; Nr4a1; glucose metabolism cardiac transcriptome analysis; high-fat diet; Nr4a1; glucose metabolism
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MDPI and ACS Style

Men, L.; Hui, W.; Guan, X.; Song, T.; Wang, X.; Zhang, S.; Chen, X. Cardiac Transcriptome Analysis Reveals Nr4a1 Mediated Glucose Metabolism Dysregulation in Response to High-Fat Diet. Genes 2020, 11, 720.

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