Bioactive Peptides and Exercise Modulate the AMPK/SIRT1/PGC-1α/FOXO3 Pathway as a Therapeutic Approach for Hypertensive Rats

Abstract

Peptides are fragments of fundamental protein sequences that may have health benefits in addition to basic dietary benefits. Recently, we have reported on the pharmacological benefits of alcalase potato protein hydrolysate (APPH) and bioactive peptides isolated from APPH. The aim was to evaluate the synergistic effect of exercise along with DIKTNKPVIF (DF) peptides in ameliorating hypertension in spontaneously hypertensive rat (SHR) rats. We examined ECG parameters, lipid profiles, cardiac markers, and histology, and quantified the proteins associated with fibrosis, hypertrophy, apoptosis, mitochondrial biogenesis, and longevity pathways. DF peptide administration, along with exercise, reduced the blood pressure and cardiac marker levels in serum. Furthermore, it also suppressed the expression of fibrosis markers COL1A1, CTGF, and uPA and downregulated cardiac-hypertrophy-associated markers such as calcineurin, NFATC3, GATA4, pGATA4 and BNP. Exercise synergistically increases the expression of IFG1, PI3K, and AKT cell-survival pathway proteins, along with DF administration. Moreover, AMPK/SIRT1/PGC-1α/FOXO3 pathway protein expression was increased with the combinatorial administration of DF and exercise. Our data suggest that exercise, along with DF peptides, act synergistically in alleviating hypertension by activating the mitochondrial biogenesis pathway.

Soybean-Derived Tripeptide Leu–Ser–Trp (LSW) Protects Human Vascular Endothelial Cells from TNFα-Induced Oxidative Stress and Inflammation via Modulating TNFα Receptors and SIRT1

“…Only a soybean-derived tetrapeptide, Val–His–Val–Val (VHVV), and another dipeptide derived from potato, Ile–Phe (IF), have recently been reported to mitigate inflammation via SIRT1 activation in spontaneously hypertensive rats [ 54 , 55 ]. Others, including three egg-derived peptides, IRW, GWN, and GW, and a potato-derived peptide, DIKTNKPVIF, could enhance mitochondrial health both in vitro and in vivo dependent on SIRT1 activation [ 56 , 57 , 58 ]. Our results demonstrate the involvement of SIRT1 in the anti-inflammatory effect of LSW, further suggesting that SIRT1 might be a potential target of bioactive peptides underlying their biological effects.…”

Microbiota dysbiosis caused by dietetic patterns as a promoter of Alzheimer's disease through metabolic syndrome mechanisms

“…AMPK-dependent phosphorylation of PGC1α results in an increased transcription of genes involved in fatty acid oxidation and mitochondrial biogenesis ( via PGC-1a/SIRT1). 108,109…”

“…AMPK-dependent phosphorylation of PGC1α results in an increased transcription of genes involved in fatty acid oxidation and mitochondrial biogenesis (via PGC-1a/SIRT1). 108,109 In addition, there are three mitochondrial sirtuins, Sirt3, Sirt4 and Sirt5 that affect cellular and organismal physiology by regulating mitochondrial functions in mammals. It seems that Sirt4-ANT2 interaction in the mitochondria is required for cellular ATP homeostasis.…”

“…Sirt4 activates a retrograde signaling response from the mitochondria to the nucleus that includes AMPK, PGC1α, key regulators of β-oxidation such as ACC, and components of the mitochondrial respiratory machinery. 109 Dysbiosis promotes the inhibition of AMPK 30 because it is down-regulated upon pro-inflammatory stimuli such as LPS and activates the expression of pro-inflammatory genes in adipose tissue. 105,107 The increased production of LPS in dysbiosis induces endotoxemia and stimulates intestinal permeability.…”