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Hesperidin ameliorates signs of the metabolic syndrome and cardiac dysfunction via IRS/Akt/GLUT4 signaling pathway in a rat model of diet-induced metabolic syndrome

European Journal of Nutrition volume 60, pages 833–848 (2021)Cite this article

Abstract

Background

Hesperidin has been reported to have biological activities such as antihypertensive, hypoglycemic, and antioxidant effects. This study investigated whether hesperidin could improve signs of the metabolic syndrome and cardiac function in a high-fat diet (HFD) induced metabolic syndrome (MS) in rats.

Methods

Male Sprague–Dawley rats were fed HFD and 15% fructose for 16 weeks and treated with hesperidin (15 or 30 mg/kg, based on signs of MS from a preliminary study) or metformin, a positive control agent, (100 mg/kg) for the final four weeks. Cardiac function, blood pressure, fasting blood glucose, oral glucose tolerance, serum insulin, and lipid profiles were measured. Histomorphometrics of left ventricles, epidydimal fat pads and liver were evaluated. Expressions of phosphorylate insulin receptor substrate1(p-IRS1), p-Akt and GLUT4 in cardiac tissue were determined.

Results

Hesperidin and metformin attenuated MS in HFD rats (p < 0.05). The accumulation of visceral fat pads and fatty liver associated with increases in liver lipid contents and liver enzymes were found in MS rats that were alleviated in hesperidin or metformin-treated groups (p < 0.05). Hesperidin and metformin improved cardiac dysfunction and hypertrophy observed in MS rats (p < 0.05). Restoration of the insulin signaling pathway, IRS/Akt/GLUT4 protein expression, was demonstrated in hesperidin and metformin-treated groups (p < 0.05). Hesperidin (30 mg/kg) was more effective than the lower dose.

Conclusion

Hesperidin was effective in reducing signs of MS and alterations of LV hypertrophy and function. These beneficial effects on the heart were associated with the restoration of the cardiac insulin signaling pathway in MS rats.

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Acknowledgements

This study is financially supported by the Scholarship for Supporting Lecturer to Admit High Potential Student to Study and Research’ on his expert program Year 2017 (Research No. 611JH216), Graduate School, Invitation Research Fund (IN63119) and Cardiovascular Research Group, Khon Kaen University, Khon Kaen, Thailand. We would like to acknowledge Prof. James A. Will, for editing the MS via Publication Clinic KKU, Thailand.

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  1. Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Patoomporn Prasatthong, Sariya Meephat, Putcharawipa Maneesai & Poungrat Pakdeechote

  2. Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Siwayu Rattanakanokchai

  3. Faculty of Medicine, Mahasarakham University, Maha Sarakham, 44000, Thailand

    Sarawoot Bunbupha

  4. Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Parichat Prachaney

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  1. Patoomporn Prasatthong
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Prasatthong, P., Meephat, S., Rattanakanokchai, S. et al. Hesperidin ameliorates signs of the metabolic syndrome and cardiac dysfunction via IRS/Akt/GLUT4 signaling pathway in a rat model of diet-induced metabolic syndrome. Eur J Nutr 60, 833–848 (2021). https://doi.org/10.1007/s00394-020-02291-4

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Keywords

  • Hesperidin
  • Cardiac function
  • Cardiac insulin signaling pathway
  • p-IRS1
  • GLUT4
  • Metabolic syndrome