1. Academic Validation
  2. Interaction between the Neuroprotective and Hyperglycemia Mitigation Effects of Walnut-Derived Peptide LVRL via the Wnt3a/β-Catenin/GSK-3β Pathway in a Type 2 Diabetes Mellitus Model

Interaction between the Neuroprotective and Hyperglycemia Mitigation Effects of Walnut-Derived Peptide LVRL via the Wnt3a/β-Catenin/GSK-3β Pathway in a Type 2 Diabetes Mellitus Model

  • J Agric Food Chem. 2024 Jul 24;72(29):16204-16220. doi: 10.1021/acs.jafc.4c01601.
Fanrui Zhao 1 2 Linxin Guo 3 Ting Huang 1 2 Chunlei Liu 3 Dan Wu 3 Li Fang 3 Weihong Min 1 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Subtropical Silviculture, Zhejiang A & F University, Hangzhou 311300, PR China.
  • 2 College of Food and Health, Zhejiang A & F University, Hangzhou 311300, PR China.
  • 3 College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, PR China.
Abstract

The term type 3 diabetes mellitus (T3DM) has been considered for Alzheimer's disease (AD) due to the common molecular and cellular characteristics found between type 2 diabetes mellitus (T2DM) and cognitive deficits. However, the specific mechanism of T3DM remains elusive, especially the neuroprotective effects of dietary components in hyperglycemic individuals. In this study, a peptide, Leu-Val-Arg-Leu (LVRL), found in walnuts significantly improved memory decline in streptozotocin (STZ)- and high-fat-diet (HFD)-stimulated T2DM mouse models (p < 0.05). The LVRL peptide also mitigated hyperglycemia, enhanced synaptic plasticity, and ameliorated mitochondrial dysfunction, as demonstrated by Morris water maze tests, immunoblotting, immunofluorescence, immunohistochemistry, transmission electron microscopy, and cellular staining. A Wnt3a inhibitor, DKK1, was subsequently used to verify the possible role of the Wnt3a/β-catenin/GSK-3β pathway in glucose-induced Insulin resistance in PC12 cells. In vitro LVRL treatment dramatically modulated the protein expression of p-Tau (Ser404), Synapsin-1, and PSD95, elevated the Insulin level, increased glucose consumption, and relieved the mitochondrial membrane potential, and MitoSOX (p < 0.05). These data suggested that Peptides like LVRL could modulate the relationship between brain Insulin and altered cognition status via the Wnt3a/β-catenin/GSK-3β pathway.

Keywords

Wnt3a/β-Catenin/GSK-3β pathway; cognitive deficiency; insulin resistance; mitochondrial function; synaptic plasticity; walnut-derived peptide.

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