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

Men, Lihui; Hui, Wenting; Guan, Xin Yuan; Song, Tongtong; Wang, Xuan; Zhang, Siwei; Chen, Xia

doi:10.3390/genes11070720

Cited by 8 publications

(6 citation statements)

References 49 publications

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“…Despite the established role of obesity in cardiovascular disease, there are limited data regarding the transcriptional effects of obesity on the heart. In a similar mouse model, existing literature has shown that obesity-induced transcriptional changes in the left ventricle largely affect genes and pathways involved in cardiac metabolism, including glycolysis as well as remodeling ( 52 ). Here we present the effects of obesity on atrial gene expression, which in particular include genes involved in cardiac metabolism, cell-cell connectivity, cardiac remodeling, and cytokine signaling.…”

Section: Discussionmentioning

confidence: 99%

Genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation

Bapat¹,

Li²,

Xiao³

et al. 2022

JCI Insight

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Obesity is an important risk factor for atrial fibrillation (AF), but a better mechanistic understanding of obesity-related atrial fibrillation is required. Serum glucocorticoid kinase 1 (SGK1) is a kinase positioned within multiple obesity-related pathways, and prior work has shown a pathologic role of SGK1 signaling in ventricular arrhythmias. We validated a mouse model of obesity-related AF using wild-type mice fed a high-fat diet. RNA sequencing of atrial tissue demonstrated substantial differences in gene expression, with enrichment of multiple SGK1-related pathways, and we showed upregulated of SGK1 transcription, activation, and signaling in obese atria. Mice expressing a cardiac specific dominant-negative SGK1 were protected from obesity-related AF, through effects on atrial electrophysiology, action potential characteristics, structural remodeling, inflammation, and sodium current. Overall, this study demonstrates the promise of targeting SGK1 in a mouse model of obesity-related AF.

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Section: Discussionmentioning

confidence: 99%

Genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation

Bapat¹,

Li²,

Xiao³

et al. 2022

JCI Insight

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“…A more recent multi-omics analysis revealed that cardiac lipid metabolism was changed in type-2 diabetic db/db mice which was supported by metabolomics and transcriptomics ( 55 ). In mice fed, an obesogenic diet global gene expression analysis revealed obesity related changes in glucose metabolism pathways ( 56 ). In line with such transcriptomic data, the proteomic results presented here confirm that obese phenotype propagates cardiac lipid utilization whilst simultaneously reducing glucose metabolism homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Proteomic and Structural Manifestations of Cardiomyopathy in Rat Models of Obesity and Weight Loss

et al. 2021

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Obesity cardiomyopathy increases the risk of heart failure and death. Obesity is curable, leading to the restoration of the heart phenotype, but it is not clear if there are any after-effects of obesity present after weight loss. We characterize the proteomic landscape of obesity cardiomyopathy with an evaluation of whether the cardiac phenotype is still shaped after weight loss. Cardiomyopathy was validated by cardiac hypertrophy, fibrosis, oversized myocytes, and mTOR upregulation in a rat model of cafeteria diet-induced developmental obesity. By global proteomic techniques (LC-MS/MS) a plethora of molecular changes was observed in the heart and circulation of obese animals, suggesting abnormal utilization of metabolic substrates. This was confirmed by increased levels of cardiac ACSL-1, a key enzyme for fatty acid degradation and decreased GLUT-1, a glucose transporter in obese rats. Calorie restriction and weight loss led to the normalization of the heart’s size, but fibrosis was still excessive. The proteomic compositions of cardiac tissue and plasma were different after weight loss as compared to control. In addition to morphological consequences, obesity cardiomyopathy involves many proteomic changes. Weight loss provides for a partial repair of the heart’s architecture, but the trace of fibrotic deposition and proteomic alterations may occur.

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“…NR4A1, regulated glycolysis and glucose transport in liver, muscle, and adipose tissue through different signaling pathway [ 18 – 20 ]. The expression of NR4A1 was downregulated in diabetic, ob/ob, and db/db mice.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome profiling of longissimus dorsi during different prenatal stages to identify genes involved in intramuscular fat deposition in lean and obese pig breeds

Chen,

Wang,

Chai

et al. 2024

Mol Biol Rep

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Background There was significant difference in muscle development between fat-type and lean-type pig breeds. Methods and results In current study, transcriptome analysis and bioinformatics analysis were used to compare the difference in longissimus dorsi (LD) muscle at three time-points (38 days post coitus (dpc), 58 dpc, and 78 dpc ) between Huainan (HN) and Large white (LW) pig breeds. A total of 24500 transcripts were obtained in 18 samples, and 2319, 2799, and 3713 differently expressed genes (DEGs) were identified between these two breeds at 38 dpc, 58 dpc, and 78 dpc, respectively. And the number and foldchange of DEGs were increased, the alternative splice also increased. The cluster analysis of DEGs indicated the embryonic development progress of LD muscle between these two breeds was different. There were 539 shared DEGs between HN and LW at three stages, and the top-shared DEGs were associated with muscle development and lipid deposition, such as KLF4, NR4A1, HSP70, ZBTB16 and so on. Conclusions The results showed DEGs between Huainan (HN) and Large white (LW) pig breeds, and contributed to the understanding the muscle development difference between HN and LW, and provided basic materials for improvement of meat quality.

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

Cited by 8 publications

References 49 publications

Genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation

Genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation

Proteomic and Structural Manifestations of Cardiomyopathy in Rat Models of Obesity and Weight Loss

Transcriptome profiling of longissimus dorsi during different prenatal stages to identify genes involved in intramuscular fat deposition in lean and obese pig breeds

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