High-fiber-diet-related metabolites improve neurodegenerative symptoms in patients with obesity with diabetes mellitus by modulating the hippocampal–hypothalamic endocrine axis
ObjectiveThrough transcriptomic and metabolomic analyses, this study examined the role of high-fiber diet in obesity complicated by diabetes and neurodegenerative symptoms.MethodThe expression matrix of high-fiber-diet-related metabolites, blood methylation profile associated with pre-symptomatic de...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2023-01-01
|
Series: | Frontiers in Neurology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2022.1026904/full |
_version_ | 1797950865974231040 |
---|---|
author | Ning Luo Yuejie Guo Lihua Peng Fangli Deng |
author_facet | Ning Luo Yuejie Guo Lihua Peng Fangli Deng |
author_sort | Ning Luo |
collection | DOAJ |
description | ObjectiveThrough transcriptomic and metabolomic analyses, this study examined the role of high-fiber diet in obesity complicated by diabetes and neurodegenerative symptoms.MethodThe expression matrix of high-fiber-diet-related metabolites, blood methylation profile associated with pre-symptomatic dementia in elderly patients with type 2 diabetes mellitus (T2DM), and high-throughput single-cell sequencing data of hippocampal samples from patients with Alzheimer's disease (AD) were retrieved from the Gene Expression Omnibus (GEO) database and through a literature search. Data were analyzed using principal component analysis (PCA) after quality control and data filtering to identify different cell clusters and candidate markers. A protein–protein interaction network was mapped using the STRING database. To further investigate the interaction among high-fiber-diet-related metabolites, methylation-related DEGs related to T2DM, and single-cell marker genes related to AD, AutoDock was used for semi-flexible molecular docking.ResultBased on GEO database data and previous studies, 24 marker genes associated with high-fiber diet, T2DM, and AD were identified. Top 10 core genes include SYNE1, ANK2, SPEG, PDZD2, KALRN, PTPRM, PTPRK, BIN1, DOCK9, and NPNT, and their functions are primarily related to autophagy. According to molecular docking analysis, acetamidobenzoic acid, the most substantially altered metabolic marker associated with a high-fiber diet, had the strongest binding affinity for SPEG.ConclusionBy targeting the SPEG protein in the hippocampus, acetamidobenzoic acid, a metabolite associated with high-fiber diet, may improve diabetic and neurodegenerative diseases in obese people. |
first_indexed | 2024-04-10T22:21:47Z |
format | Article |
id | doaj.art-452decdc6d6649579f92e715f0164e83 |
institution | Directory Open Access Journal |
issn | 1664-2295 |
language | English |
last_indexed | 2024-04-10T22:21:47Z |
publishDate | 2023-01-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Neurology |
spelling | doaj.art-452decdc6d6649579f92e715f0164e832023-01-17T14:51:41ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-01-011310.3389/fneur.2022.10269041026904High-fiber-diet-related metabolites improve neurodegenerative symptoms in patients with obesity with diabetes mellitus by modulating the hippocampal–hypothalamic endocrine axisNing Luo0Yuejie Guo1Lihua Peng2Fangli Deng3Department of Endocrinology, Chenzhou No. 1 People's Hospital, Chenzhou, ChinaDepartment of Geriatrics, Chenzhou No. 1 People's Hospital, Chenzhou, ChinaDepartment of Clinical Laboratory, Chenzhou No. 4 People's Hospital, Chenzhou, ChinaBreast Health Care Center, Chenzhou No. 1 People's Hospital, Chenzhou, ChinaObjectiveThrough transcriptomic and metabolomic analyses, this study examined the role of high-fiber diet in obesity complicated by diabetes and neurodegenerative symptoms.MethodThe expression matrix of high-fiber-diet-related metabolites, blood methylation profile associated with pre-symptomatic dementia in elderly patients with type 2 diabetes mellitus (T2DM), and high-throughput single-cell sequencing data of hippocampal samples from patients with Alzheimer's disease (AD) were retrieved from the Gene Expression Omnibus (GEO) database and through a literature search. Data were analyzed using principal component analysis (PCA) after quality control and data filtering to identify different cell clusters and candidate markers. A protein–protein interaction network was mapped using the STRING database. To further investigate the interaction among high-fiber-diet-related metabolites, methylation-related DEGs related to T2DM, and single-cell marker genes related to AD, AutoDock was used for semi-flexible molecular docking.ResultBased on GEO database data and previous studies, 24 marker genes associated with high-fiber diet, T2DM, and AD were identified. Top 10 core genes include SYNE1, ANK2, SPEG, PDZD2, KALRN, PTPRM, PTPRK, BIN1, DOCK9, and NPNT, and their functions are primarily related to autophagy. According to molecular docking analysis, acetamidobenzoic acid, the most substantially altered metabolic marker associated with a high-fiber diet, had the strongest binding affinity for SPEG.ConclusionBy targeting the SPEG protein in the hippocampus, acetamidobenzoic acid, a metabolite associated with high-fiber diet, may improve diabetic and neurodegenerative diseases in obese people.https://www.frontiersin.org/articles/10.3389/fneur.2022.1026904/fullhigh-fiber dietneurodegenerative diseasesobesityneurovascularSPEGAD |
spellingShingle | Ning Luo Yuejie Guo Lihua Peng Fangli Deng High-fiber-diet-related metabolites improve neurodegenerative symptoms in patients with obesity with diabetes mellitus by modulating the hippocampal–hypothalamic endocrine axis Frontiers in Neurology high-fiber diet neurodegenerative diseases obesity neurovascular SPEG AD |
title | High-fiber-diet-related metabolites improve neurodegenerative symptoms in patients with obesity with diabetes mellitus by modulating the hippocampal–hypothalamic endocrine axis |
title_full | High-fiber-diet-related metabolites improve neurodegenerative symptoms in patients with obesity with diabetes mellitus by modulating the hippocampal–hypothalamic endocrine axis |
title_fullStr | High-fiber-diet-related metabolites improve neurodegenerative symptoms in patients with obesity with diabetes mellitus by modulating the hippocampal–hypothalamic endocrine axis |
title_full_unstemmed | High-fiber-diet-related metabolites improve neurodegenerative symptoms in patients with obesity with diabetes mellitus by modulating the hippocampal–hypothalamic endocrine axis |
title_short | High-fiber-diet-related metabolites improve neurodegenerative symptoms in patients with obesity with diabetes mellitus by modulating the hippocampal–hypothalamic endocrine axis |
title_sort | high fiber diet related metabolites improve neurodegenerative symptoms in patients with obesity with diabetes mellitus by modulating the hippocampal hypothalamic endocrine axis |
topic | high-fiber diet neurodegenerative diseases obesity neurovascular SPEG AD |
url | https://www.frontiersin.org/articles/10.3389/fneur.2022.1026904/full |
work_keys_str_mv | AT ningluo highfiberdietrelatedmetabolitesimproveneurodegenerativesymptomsinpatientswithobesitywithdiabetesmellitusbymodulatingthehippocampalhypothalamicendocrineaxis AT yuejieguo highfiberdietrelatedmetabolitesimproveneurodegenerativesymptomsinpatientswithobesitywithdiabetesmellitusbymodulatingthehippocampalhypothalamicendocrineaxis AT lihuapeng highfiberdietrelatedmetabolitesimproveneurodegenerativesymptomsinpatientswithobesitywithdiabetesmellitusbymodulatingthehippocampalhypothalamicendocrineaxis AT fanglideng highfiberdietrelatedmetabolitesimproveneurodegenerativesymptomsinpatientswithobesitywithdiabetesmellitusbymodulatingthehippocampalhypothalamicendocrineaxis |