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Integrative proteomic network analyses support depot-specific roles for leucine rich repeat LGI family member 3 in adipose tissues
LGI family member 3 (LGI3) is a member of the LGI protein family. In our previous studies, LGI3 was determined to be expressed in adipose tissues, skin and the brain, where it served as a pleiotropic cytokine. The results indicated that LGI3 levels are increased in adipose tissues of obese individua...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200805/ https://www.ncbi.nlm.nih.gov/pubmed/34149883 http://dx.doi.org/10.3892/etm.2021.10269 |
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author | Kim, Hyun A. Baek, Kwang Jin Yun, Hye-Young |
author_facet | Kim, Hyun A. Baek, Kwang Jin Yun, Hye-Young |
author_sort | Kim, Hyun A. |
collection | PubMed |
description | LGI family member 3 (LGI3) is a member of the LGI protein family. In our previous studies, LGI3 was determined to be expressed in adipose tissues, skin and the brain, where it served as a pleiotropic cytokine. The results indicated that LGI3 levels are increased in adipose tissues of obese individuals in comparison with control individuals and that LGI3 suppressed adipogenesis via its receptor, disintegrin and metalloproteinase domain-containing protein 23. Additionally, it was reported that LGI3 upregulates tumor necrosis factor-α and downregulated adiponectin and hypothesized that LGI3 may act as a proinflammatory adipokine involved in adipose tissue inflammation. In the present study, cytokine arrays were used to analyze cytokine levels in adipose tissues and plasma of LGI3-knockout mice and signaling protein arrays used to analyze the expression and phosphorylation of these proteins in LGI3-treated preadipocytes. The results suggested that expression levels of 129 gene products (24 cytokines and 105 signaling proteins) were altered in response to LGI3 deficiency or LGI3 treatment, respectively. Protein-protein interaction network analysis of LGI3-regulated gene products revealed that 94% of the gene products (21 cytokines and 100 signaling proteins) formed an interaction network cluster. Functional enrichment analysis for the LGI3-regulated gene products, including those from our previous studies, revealed an association with numerous biological processes, including inflammatory responses, cellular differentiation and development and metabolic regulation. Gene co-expression network analysis revealed that these LGI3-regulated gene products were involved in various biological processes in an overlapping and differential manner between subcutaneous and visceral adipose tissues. Notably, inflammatory responses were more strongly associated with the LGI3-regulated gene co-expression network in visceral adipose tissues than in subcutaneous adipose tissues. Analysis of expression quantitative trait loci identified four single nucleotide variants that affect expression of LGI3 in an adipose depot-specific manner. Taken together, the results suggested that LGI3 may serve depot-specific roles as an adipokine in adipose tissues. |
format | Online Article Text |
id | pubmed-8200805 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-82008052021-06-17 Integrative proteomic network analyses support depot-specific roles for leucine rich repeat LGI family member 3 in adipose tissues Kim, Hyun A. Baek, Kwang Jin Yun, Hye-Young Exp Ther Med Articles LGI family member 3 (LGI3) is a member of the LGI protein family. In our previous studies, LGI3 was determined to be expressed in adipose tissues, skin and the brain, where it served as a pleiotropic cytokine. The results indicated that LGI3 levels are increased in adipose tissues of obese individuals in comparison with control individuals and that LGI3 suppressed adipogenesis via its receptor, disintegrin and metalloproteinase domain-containing protein 23. Additionally, it was reported that LGI3 upregulates tumor necrosis factor-α and downregulated adiponectin and hypothesized that LGI3 may act as a proinflammatory adipokine involved in adipose tissue inflammation. In the present study, cytokine arrays were used to analyze cytokine levels in adipose tissues and plasma of LGI3-knockout mice and signaling protein arrays used to analyze the expression and phosphorylation of these proteins in LGI3-treated preadipocytes. The results suggested that expression levels of 129 gene products (24 cytokines and 105 signaling proteins) were altered in response to LGI3 deficiency or LGI3 treatment, respectively. Protein-protein interaction network analysis of LGI3-regulated gene products revealed that 94% of the gene products (21 cytokines and 100 signaling proteins) formed an interaction network cluster. Functional enrichment analysis for the LGI3-regulated gene products, including those from our previous studies, revealed an association with numerous biological processes, including inflammatory responses, cellular differentiation and development and metabolic regulation. Gene co-expression network analysis revealed that these LGI3-regulated gene products were involved in various biological processes in an overlapping and differential manner between subcutaneous and visceral adipose tissues. Notably, inflammatory responses were more strongly associated with the LGI3-regulated gene co-expression network in visceral adipose tissues than in subcutaneous adipose tissues. Analysis of expression quantitative trait loci identified four single nucleotide variants that affect expression of LGI3 in an adipose depot-specific manner. Taken together, the results suggested that LGI3 may serve depot-specific roles as an adipokine in adipose tissues. D.A. Spandidos 2021-08 2021-06-04 /pmc/articles/PMC8200805/ /pubmed/34149883 http://dx.doi.org/10.3892/etm.2021.10269 Text en Copyright: © Kim et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Kim, Hyun A. Baek, Kwang Jin Yun, Hye-Young Integrative proteomic network analyses support depot-specific roles for leucine rich repeat LGI family member 3 in adipose tissues |
title | Integrative proteomic network analyses support depot-specific roles for leucine rich repeat LGI family member 3 in adipose tissues |
title_full | Integrative proteomic network analyses support depot-specific roles for leucine rich repeat LGI family member 3 in adipose tissues |
title_fullStr | Integrative proteomic network analyses support depot-specific roles for leucine rich repeat LGI family member 3 in adipose tissues |
title_full_unstemmed | Integrative proteomic network analyses support depot-specific roles for leucine rich repeat LGI family member 3 in adipose tissues |
title_short | Integrative proteomic network analyses support depot-specific roles for leucine rich repeat LGI family member 3 in adipose tissues |
title_sort | integrative proteomic network analyses support depot-specific roles for leucine rich repeat lgi family member 3 in adipose tissues |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200805/ https://www.ncbi.nlm.nih.gov/pubmed/34149883 http://dx.doi.org/10.3892/etm.2021.10269 |
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