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

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.

In vitro and in silico characterization of adiponectin-receptor agonist dipeptides.

The aim of this study is to develop a dipeptide showing an adiponectin receptor 1 (AdipoR1) agonistic effect in skeletal muscle L6 myotubes. Based on the structure of the AdipoR1 agonist, AdipoRon, 15 synthetic dipeptides were targeted to promote glucose uptake in L6 myotubes. Tyr-Pro showed a significant increase in glucose uptake among the dipeptides, while other dipeptides, including Pro-Tyr, failed to exert this effect. Tyr-Pro induces glucose transporter 4 (Glut4) expression in the plasma membrane, along with adenosine monophosphate-activated protein kinase (AMPK) activation. In AdipoR1-knocked down cells, the promotion by Tyr-Pro was ameliorated, indicating that Tyr-Pro may directly interact with AdipoR1 as an agonist, followed by the activation of AMPK/Glut4 translocation in L6 myotubes. Molecular dynamics simulations revealed that a Tyr-Pro molecule was stably positioned in the two potential binding pockets (sites 1 and 2) of the seven-transmembrane receptor, AdipoR1, anchored in a virtual 1-palmitoyl-2-oleoyl-phosphatidylcholine membrane. In conclusion, we demonstrated the antidiabetic function of the Tyr-Pro dipeptide as a possible AdipoR1 agonist.

Brain-transportable soy dipeptide, Tyr-Pro, attenuates amyloid ß peptide25-35-induced memory impairment in mice.

In this study, experiments on amyloid ß peptide25-35-induced mice were performed to provide in vivo evidence on the potential of the blood-brain barrier transportable soy dipeptide, Tyr-Pro, in combating memory impairment. We demonstrated for the first time that oral administration of Tyr-Pro (100 mg/kg, twice a day) in mice for 16 days significantly improved impaired memory by spontaneous alternation and shortened step-through latency in amyloid ß-induced mice.

Self-organization phenomena and decaying self-similar state in two-dimensional incompressible viscous fluids.

The final self-similar state of decaying two-dimensional (2D) turbulence in 2D incompressible viscous flow is analytically and numerically investigated for the case with periodic boundaries. It is proved by theoretical analysis and simulations that the sinh-Poisson state comega=-sinh (betapsi) is not realized in the dynamical system of interest. It is shown by an eigenfunction spectrum analysis that a sufficient explanation for the self-organization to the decaying self-similar state is the faster energy decay of higher eigenmodes and the energy accumulation to the lowest eigenmode for given boundary conditions due to simultaneous normal and inverse cascading by nonlinear mode couplings. The theoretical prediction is demonstrated to be correct by simulations leading to the lowest eigenmode of {(1,0) + (0,1)} of the dissipative operator for the periodic boundaries. It is also clarified that an important process during nonlinear self-organization is an interchange between the dominant operators, which leads to the final decaying self-similar state.