Fanrui Zhao, Linxin Guo, Ting Huang, Chunlei Liu, Dan Wu, Li Fang, Weihong Min
{"title":"核桃提取物肽 LVRL 通过 Wnt3a/β-Catenin/GSK-3β 通路在 2 型糖尿病模型中的神经保护作用与高血糖缓解作用之间的相互作用","authors":"Fanrui Zhao, Linxin Guo, Ting Huang, Chunlei Liu, Dan Wu, Li Fang, Weihong Min","doi":"10.1021/acs.jafc.4c01601","DOIUrl":null,"url":null,"abstract":"<p><p>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 (<i>p</i> < 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. <i>In vitro</i> 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 (<i>p</i> < 0.05). These data suggested that peptides like LVRL could modulate the relationship between brain insulin and altered cognition status <i>via</i> the Wnt3a/β-Catenin/GSK-3β pathway.</p>","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":null,"pages":null},"PeriodicalIF":5.7000,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Interaction between the Neuroprotective and Hyperglycemia Mitigation Effects of Walnut-Derived Peptide LVRL <i>via</i> the Wnt3a/β-Catenin/GSK-3β Pathway in a Type 2 Diabetes Mellitus Model.\",\"authors\":\"Fanrui Zhao, Linxin Guo, Ting Huang, Chunlei Liu, Dan Wu, Li Fang, Weihong Min\",\"doi\":\"10.1021/acs.jafc.4c01601\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 (<i>p</i> < 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. <i>In vitro</i> 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 (<i>p</i> < 0.05). These data suggested that peptides like LVRL could modulate the relationship between brain insulin and altered cognition status <i>via</i> the Wnt3a/β-Catenin/GSK-3β pathway.</p>\",\"PeriodicalId\":41,\"journal\":{\"name\":\"Journal of Agricultural and Food Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2024-07-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Agricultural and Food Chemistry\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.jafc.4c01601\",\"RegionNum\":1,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/10 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"AGRICULTURE, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Agricultural and Food Chemistry","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1021/acs.jafc.4c01601","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/10 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"AGRICULTURE, MULTIDISCIPLINARY","Score":null,"Total":0}
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.
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.
期刊介绍:
The Journal of Agricultural and Food Chemistry publishes high-quality, cutting edge original research representing complete studies and research advances dealing with the chemistry and biochemistry of agriculture and food. The Journal also encourages papers with chemistry and/or biochemistry as a major component combined with biological/sensory/nutritional/toxicological evaluation related to agriculture and/or food.