In Vitro and in Silico Analyses of the Adiponectin Receptor Agonistic Action of Soybean Tripeptides

Abstract

The Tyr-Pro (YP) dipeptide can serve as an adiponectin receptor 1 (AdipoR1) agonist. We thus investigated the AdipoR1-agonistic potential of YP-related tripeptides in the soybean protein sequence. Among the 17 soybean candidate tripeptides, those elongated at the C-terminus of YP (0.1 μM YPG, 140 ± 16%; 0.1 μM YPE, 141 ± 22%; 0.1 μM YPP, 145 ± 19%; 0.1 μM YPQ, 143 ± 20%; p < 0.05) significantly promoted glucose uptake by L6 muscle myotubes, comparable to the effect of 0.1 μM AdipoRon (163 ± 52%, p < 0.05). The knockdown of AdipoR1 expression in L6 cells abrogated this effect of YPG and YPP, indicating that the two tripeptides had an AdipoR1 agonistic effect. CHARMM-GUI-aided molecular dynamics simulation in a virtual phospholipid membrane revealed that YPG and YPP were stably positioned at the binding pockets of AdipoR1 (binding free energy < −10 kcal/mol). These findings demonstrate that the tripeptides YPG and YPP, with AdipoR1 agonistic YP sequences, have alternative adiponectin-like potential via their preferential binding to AdipoR1.

Adiponectin-Receptor Agonistic Dipeptide Tyr–Pro Stimulates the Acetylcholine Nervous System in NE-4C Cells

“…To date, there have been no reports on natural AdipoR1 agonists, except for our previous studies where peptides, including Tyr−Pro, interacted with AdipoR1 in skeletal muscle cell line experiments and by in silico molecular docking simulation analysis. 8,21 Our subsequent studies demonstrated that Tyr−Pro has brain-beneficial effects through intact BBB transport and accumulation in the mouse brain parenchyma 7 and by improving long-term memory impairment in Aβ-induced acute AD mice. 6 In acute AD mouse experiments, we found that a 2 week administration of Tyr−Pro resulted in a significant increase in ChAT expression in the cerebral cortex region.…”

Molecular Dynamics Simulations Help Determine the Molecular Mechanisms of Lasioglossin-III and Its Variant Peptides’ Membrane Interfacial Interactions

“…The results indicate that all the peptides exhibited stable binding with the bacterial membranes. 23 Interestingly, WT peptide P1 possessed similar affinities toward gram −ve and gram +ve bacterial membranes, as did peptide P3. However, the most interesting observation was the binding affinity of the P2 peptide.…”

“…The equation used was normalΔ G normalb normali normaln normald = G normalc normalo normalm normalp normall normale normalx − ( G m e m b r a n e + G p e p t i d e ) where G complex represents the total free energy of the membrane–peptide complex in the water system, and G membrane and G peptide represent the total free energies of the separated membrane and peptide, respectively. Only the enthalpic components were considered in the computational estimation …”

“…Only the enthalpic components were considered in the computational estimation. 23 Antibacterial Assay of Peptides. Antibacterial assays for the desired peptides were done using the diffusion method.…”

Drug targets regulate systemic metabolism and provide new horizons to treat nonalcoholic steatohepatitis

“…Besides AdipoRon derivatives, oligopeptides also reveal promising anti-NASH potencies. For instance, tripeptides from soybean activate AdipoR1 and their anti-NASH potencies are expected to be investigated in the future [ 146 ]. Moreover, AdipoR1/AdipoR2 dual agonist JT003 activates both AdipoR1/AdipoR2, as well as AMPK, PPARα, and PI3K-Akt pathways.…”