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Molecular mechanisms underlying hypertensive effect of fructose and the preventive properties of inulin – Global transcriptomic analysis in rat aorta

Published:November 10, 2022DOI:https://doi.org/10.1016/j.numecd.2022.11.009
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      Highlights

      • Fructose-based diet impacts global transcriptome in rat aorta.
      • Partial substitution of dietary fructose with inulin counteracts the observed effects on global aorta transcriptome.
      • Modulated genes are involved in vascular and endothelial functions, cell signaling, or cellular metabolism.
      • Potential transcription factors and miRNAs regulating the expression of affected genes are identified.
      • Bioinformatic analyses of transcriptomic data identified relevant molecular mechanisms underlying the anti-hypertensive property of inulin.

      Abstract

      Background and Aims

      Excessive intake of fructose is a significant contributor in the development of hypertension and pathogenesis of cardiometabolic diseases. We previously showed that dietary inulin can prevent fructose-induced hypertension in rats. Nevertheless, molecular mechanisms of both fructose and inulin in aorta remain unknown. The aim of this study was to identify global transcriptomic changes in aorta in rats on fructose-based diet or partial substitution of dietary fructose with inulin.

      Methods and Results

      At the end of study periods, aortas were isolated, RNA extracted, and transcriptomics performed using microarrays followed by in-dept bioinformatic analyses. We observed that fructose-based diet affected the expression of over 1700 genes involved in the regulation of vascular functions, cell signaling, and cellular metabolism. Partial substitution of dietary fructose with inulin affected the expression of over 1300 genes regulating endothelial and vascular functions, including relaxin signaling pathway, immune/inflammatory response, or cellular metabolism. Bioinformatic analyses revealed transcription factors, such as Junb or Nr4a2, and miRNAs, such as miR-206, miR-137 or miR-375, as potential transcriptional and post-transcriptional regulators of identified differentially expressed genes. Genes identified following both diets are associated with development of cardiovascular diseases, hypertension, immune system diseases and metabolic diseases. Moreover, a negative correlation between the expression profiles obtained by fructose-based diet and that by partial substitution of dietary fructose with inulin was observed.

      Conclusion

      Our study showed that fructose can significantly impact global transcriptomic profile in aorta, changes that can be counteracted by inulin and which present relevant molecular mechanisms underlying its anti-hypertensive property.

      Keywords

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