Adipose Tissue Caveolin-1 Upregulation in Obesity Involves TNF-α/NF-κB Mediated Signaling
Obesity is characterized by chronic low-grade inflammation. Obese people have higher levels of caveolin-1 (CAV1), a structural and functional protein present in adipose tissues (ATs). We aimed to define the inflammatory mediators that influence <i>CAV1</i> gene regulation and the associa...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/7/1019 |
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| author | Ashraf Al Madhoun Shihab Kochumon Dania Haddad Reeby Thomas Rasheeba Nizam Lavina Miranda Sardar Sindhu Milad S. Bitar Rasheed Ahmad Fahd Al-Mulla |
| author_facet | Ashraf Al Madhoun Shihab Kochumon Dania Haddad Reeby Thomas Rasheeba Nizam Lavina Miranda Sardar Sindhu Milad S. Bitar Rasheed Ahmad Fahd Al-Mulla |
| author_sort | Ashraf Al Madhoun |
| collection | DOAJ |
| description | Obesity is characterized by chronic low-grade inflammation. Obese people have higher levels of caveolin-1 (CAV1), a structural and functional protein present in adipose tissues (ATs). We aimed to define the inflammatory mediators that influence <i>CAV1</i> gene regulation and the associated mechanisms in obesity. Using subcutaneous AT from 27 (7 lean and 20 obese) normoglycemic individuals, in vitro human adipocyte models, and in vivo mice models, we found elevated CAV1 expression in obese AT and a positive correlation between the gene expression of CAV1, tumor necrosis factor-alpha (TNF-α), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). <i>CAV1</i> gene expression was associated with proinflammatory cytokines and chemokines and their cognate receptors (<i>r</i> ≥ 0.447, <i>p</i> ≤ 0.030), but not with anti-inflammatory markers. <i>CAV1</i> expression was correlated with CD163, indicating a prospective role for CAV1 in the adipose inflammatory microenvironment. Unlike wild-type animals, mice lacking TNF-α exhibited reduced levels of CAV1 mRNA/proteins, which were elevated by administering exogenous TNF-α. Mechanistically, TNF-α induces <i>CAV1</i> gene transcription by mediating NF-κB binding to its two regulatory elements located in the CAV1 proximal regulatory region. The interplay between CAV1 and the TNF-α signaling pathway is intriguing and has potential as a target for therapeutic interventions in obesity and metabolic syndromes. |
| first_indexed | 2024-03-11T05:40:31Z |
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| id | doaj.art-2128cbf639a34dab9b3011ac0e2ae6d7 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T05:40:31Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2128cbf639a34dab9b3011ac0e2ae6d72023-11-17T16:28:09ZengMDPI AGCells2073-44092023-03-01127101910.3390/cells12071019Adipose Tissue Caveolin-1 Upregulation in Obesity Involves TNF-α/NF-κB Mediated SignalingAshraf Al Madhoun0Shihab Kochumon1Dania Haddad2Reeby Thomas3Rasheeba Nizam4Lavina Miranda5Sardar Sindhu6Milad S. Bitar7Rasheed Ahmad8Fahd Al-Mulla9Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15462, KuwaitImmunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, KuwaitGenetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15462, KuwaitImmunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, KuwaitGenetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15462, KuwaitAnimal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman 15462, KuwaitAnimal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman 15462, KuwaitGenetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15462, KuwaitImmunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, KuwaitGenetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15462, KuwaitObesity is characterized by chronic low-grade inflammation. Obese people have higher levels of caveolin-1 (CAV1), a structural and functional protein present in adipose tissues (ATs). We aimed to define the inflammatory mediators that influence <i>CAV1</i> gene regulation and the associated mechanisms in obesity. Using subcutaneous AT from 27 (7 lean and 20 obese) normoglycemic individuals, in vitro human adipocyte models, and in vivo mice models, we found elevated CAV1 expression in obese AT and a positive correlation between the gene expression of CAV1, tumor necrosis factor-alpha (TNF-α), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). <i>CAV1</i> gene expression was associated with proinflammatory cytokines and chemokines and their cognate receptors (<i>r</i> ≥ 0.447, <i>p</i> ≤ 0.030), but not with anti-inflammatory markers. <i>CAV1</i> expression was correlated with CD163, indicating a prospective role for CAV1 in the adipose inflammatory microenvironment. Unlike wild-type animals, mice lacking TNF-α exhibited reduced levels of CAV1 mRNA/proteins, which were elevated by administering exogenous TNF-α. Mechanistically, TNF-α induces <i>CAV1</i> gene transcription by mediating NF-κB binding to its two regulatory elements located in the CAV1 proximal regulatory region. The interplay between CAV1 and the TNF-α signaling pathway is intriguing and has potential as a target for therapeutic interventions in obesity and metabolic syndromes.https://www.mdpi.com/2073-4409/12/7/1019caveolin-1obesityadipose tissuemetabolic inflammationcytokinesTNF-α |
| spellingShingle | Ashraf Al Madhoun Shihab Kochumon Dania Haddad Reeby Thomas Rasheeba Nizam Lavina Miranda Sardar Sindhu Milad S. Bitar Rasheed Ahmad Fahd Al-Mulla Adipose Tissue Caveolin-1 Upregulation in Obesity Involves TNF-α/NF-κB Mediated Signaling Cells caveolin-1 obesity adipose tissue metabolic inflammation cytokines TNF-α |
| title | Adipose Tissue Caveolin-1 Upregulation in Obesity Involves TNF-α/NF-κB Mediated Signaling |
| title_full | Adipose Tissue Caveolin-1 Upregulation in Obesity Involves TNF-α/NF-κB Mediated Signaling |
| title_fullStr | Adipose Tissue Caveolin-1 Upregulation in Obesity Involves TNF-α/NF-κB Mediated Signaling |
| title_full_unstemmed | Adipose Tissue Caveolin-1 Upregulation in Obesity Involves TNF-α/NF-κB Mediated Signaling |
| title_short | Adipose Tissue Caveolin-1 Upregulation in Obesity Involves TNF-α/NF-κB Mediated Signaling |
| title_sort | adipose tissue caveolin 1 upregulation in obesity involves tnf α nf κb mediated signaling |
| topic | caveolin-1 obesity adipose tissue metabolic inflammation cytokines TNF-α |
| url | https://www.mdpi.com/2073-4409/12/7/1019 |
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