Comprehensive microarray analysis for the identification of therapeutic targets within HIF-1α signalling networks in diet-induced obesity via hypothalamic inflammation.
Hai Guo, Lijuan Ma, Dilihumaier Duolikun, Qiaoling Yao
{"title":"Comprehensive microarray analysis for the identification of therapeutic targets within HIF-1α signalling networks in diet-induced obesity via hypothalamic inflammation.","authors":"Hai Guo, Lijuan Ma, Dilihumaier Duolikun, Qiaoling Yao","doi":"10.20945/2359-4292-2024-0098","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>A high-fat diet (HFD) significantly contributes to obesity and alters the neurological function of the brain. This study explored the influence of hypoxia-inducible factor (HIF-1) and its downstream molecules on obesity progression in the context of HFD-induced hypothalamic inflammation.</p><p><strong>Materials and methods: </strong>Utilizing a bioinformatics approach alongside animal models, targets and pathways related to hypothalamic obesity were identified via network analysis, gene target identification, gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and subsequent validation in animal models.</p><p><strong>Results: </strong>HIF-1α has the potential to regulate the immune response by promoting immune infiltration and increasing the population of immune cells, particularly memory CD4 T cells, in the hypothalamus, primarily through its influence on ksr2 expression. Additionally, the analysis predicted five drugs capable of enhancing HIF-1-Ksr2 signalling.</p><p><strong>Conclusion: </strong>In conclusion, targeting Ksr2 with specific drugs represents a potential approach for addressing HFD-induced obesity. These novel findings lay the groundwork for developing dietary supplements and therapeutic interventions.</p>","PeriodicalId":54303,"journal":{"name":"Archives of Endocrinology Metabolism","volume":"69 1","pages":"e240098"},"PeriodicalIF":1.6000,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895521/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Endocrinology Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.20945/2359-4292-2024-0098","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: A high-fat diet (HFD) significantly contributes to obesity and alters the neurological function of the brain. This study explored the influence of hypoxia-inducible factor (HIF-1) and its downstream molecules on obesity progression in the context of HFD-induced hypothalamic inflammation.
Materials and methods: Utilizing a bioinformatics approach alongside animal models, targets and pathways related to hypothalamic obesity were identified via network analysis, gene target identification, gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and subsequent validation in animal models.
Results: HIF-1α has the potential to regulate the immune response by promoting immune infiltration and increasing the population of immune cells, particularly memory CD4 T cells, in the hypothalamus, primarily through its influence on ksr2 expression. Additionally, the analysis predicted five drugs capable of enhancing HIF-1-Ksr2 signalling.
Conclusion: In conclusion, targeting Ksr2 with specific drugs represents a potential approach for addressing HFD-induced obesity. These novel findings lay the groundwork for developing dietary supplements and therapeutic interventions.
期刊介绍:
The Archives of Endocrinology and Metabolism - AE&M – is the official journal of the Brazilian Society of Endocrinology and Metabolism - SBEM, which is affiliated with the Brazilian Medical Association.
Edited since 1951, the AE&M aims at publishing articles on scientific themes in the basic translational and clinical area of Endocrinology and Metabolism. The printed version AE&M is published in 6 issues/year. The full electronic issue is open access in the SciELO - Scientific Electronic Library Online e at the AE&M site: www.aem-sbem.com.
From volume 59 on, the name was changed to Archives of Endocrinology and Metabolism, and it became mandatory for manuscripts to be submitted in English for the online issue. However, for the printed issue it is still optional for the articles to be sent in English or Portuguese.
The journal is published six times a year, with one issue every two months.