Dipeptide IF and Exercise Training Attenuate Hypertension in SHR Rats by Inhibiting Fibrosis and Hypertrophy and Activating AMPKα1, SIRT1, and PGC1α

Int J Mol Sci. 2022 Jul 25;23(15):8167. doi: 10.3390/ijms23158167.

Abstract

Bioactive peptides are physiologically active peptides produced from proteins by gastrointestinal digestion, fermentation, or hydrolysis by proteolytic enzymes. Bioactive peptides are resorbed in their whole form and have a preventive effect against various disease conditions, including hypertension, dyslipidemia, inflammation, and oxidative stress. In recent years, there has been a growing body of evidence showing that physiologically active peptides may have a function in sports nutrition. The present study aimed to evaluate the synergistic effect of dipeptide (IF) from alcalase potato protein hydrolysates and exercise training in hypertensive (SHR) rats. Animals were divided into five groups. Bioactive peptide IF and swimming exercise training normalized the blood pressure and decreased the heart weight. Cardiac, hepatic, and renal functional markers also normalized in SHR rats. The combined administration of IF peptide and exercise offer better protection in SHR rats by downregulating proteins associated with myocardial fibrosis, hypertrophy, and inflammation. Remarkably, peptide treatment alongside exercise activates the PI3K/AKT cell survival pathway in the myocardial tissue of SHR animals. Further, the mitochondrial biogenesis pathway (AMPKα1, SIRT1, and PGC1α) was synergistically activated by the combinatorial treatment of IF and exercise. Exercise training along with IF administration could be a possible approach to alleviating hypertension.

Keywords: bioactive peptide; exercise training; fibrosis; hypertension; hypertrophy.

MeSH terms

  • Animals
  • Blood Pressure
  • Dipeptides / pharmacology
  • Fibrosis
  • Hypertension* / metabolism
  • Hypertrophy / metabolism
  • Inflammation / pathology
  • Myocardium / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Physical Conditioning, Animal* / physiology
  • Rats
  • Rats, Inbred SHR
  • Sirtuin 1 / metabolism
  • Swimming

Substances

  • Dipeptides
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Sirt1 protein, rat
  • Sirtuin 1