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. 2021 Mar;60(2):833-848. doi: 10.1007/s00394-020-02291-4. Epub 2020 May 27.

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.

Keywords: Cardiac function; Cardiac insulin signaling pathway; GLUT4; Hesperidin; Metabolic syndrome; p-IRS1.

MeSH terms

  • Animals
  • Blood Glucose
  • Diet, High-Fat / adverse effects
  • Glucose Transporter Type 4 / genetics
  • Heart Diseases* / drug therapy
  • Hesperidin* / pharmacology
  • Insulin / metabolism
  • Insulin Resistance*
  • Male
  • Metabolic Syndrome* / drug therapy
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction

Substances

  • Blood Glucose
  • Glucose Transporter Type 4
  • Insulin
  • Hesperidin
  • Proto-Oncogene Proteins c-akt