Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice
Abstract During recent decades, changes in lifestyle have led to widespread nutritional obesity and its related complications. Remodelling adipose tissue as a therapeutic goal for obesity and its complications has attracted much attention and continues to be actively explored. The endothelium lines...
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| Format: | Article |
| Language: | English |
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2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54669-1 |
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| author | Cheukyau Luk Katherine I. Bridge Nele Warmke Katie J. Simmons Michael Drozd Amy Moran Amanda D. V. MacCannell Chew W. Cheng Sam Straw Jason L. Scragg Jessica Smith Claire H. Ozber Chloe G. Wilkinson Anna Skromna Natallia Makava Hiran A. Prag T. Simon Futers Oliver I. Brown Alexander-Francisco Bruns Andrew MN Walker Nicole T. Watt Romana Mughal Kathryn J. Griffin Nadira Y. Yuldasheva Sunti Limumpornpetch Hema Viswambharan Piruthivi Sukumar David J. Beech Antonio Vidal-Puig Klaus K. Witte Michael P. Murphy Richard C. Hartley Stephen B. Wheatcroft Richard M. Cubbon Lee D. Roberts Mark T. Kearney Natalie J. Haywood |
| author_facet | Cheukyau Luk Katherine I. Bridge Nele Warmke Katie J. Simmons Michael Drozd Amy Moran Amanda D. V. MacCannell Chew W. Cheng Sam Straw Jason L. Scragg Jessica Smith Claire H. Ozber Chloe G. Wilkinson Anna Skromna Natallia Makava Hiran A. Prag T. Simon Futers Oliver I. Brown Alexander-Francisco Bruns Andrew MN Walker Nicole T. Watt Romana Mughal Kathryn J. Griffin Nadira Y. Yuldasheva Sunti Limumpornpetch Hema Viswambharan Piruthivi Sukumar David J. Beech Antonio Vidal-Puig Klaus K. Witte Michael P. Murphy Richard C. Hartley Stephen B. Wheatcroft Richard M. Cubbon Lee D. Roberts Mark T. Kearney Natalie J. Haywood |
| author_sort | Cheukyau Luk |
| collection | DOAJ |
| description | Abstract During recent decades, changes in lifestyle have led to widespread nutritional obesity and its related complications. Remodelling adipose tissue as a therapeutic goal for obesity and its complications has attracted much attention and continues to be actively explored. The endothelium lines all blood vessels and is close to all cells, including adipocytes. The endothelium has been suggested to act as a paracrine organ. We explore the role of endothelial insulin-like growth factor-1 receptor (IGF-1R), as a paracrine modulator of white adipose phenotype. We show that a reduction in endothelial IGF-1R expression in the presence of high-fat feeding in male mice leads to depot-specific beneficial white adipose tissue remodelling, increases whole-body energy expenditure and enhances insulin sensitivity via a non-cell-autonomous paracrine mechanism. We demonstrate that increased endothelial malonate may be contributory and that malonate prodrugs have potentially therapeutically relevant properties in the treatment of obesity-related metabolic disease. |
| format | Article |
| id | doaj-art-d77e74ff3433493a95b24c364e6056f9 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d77e74ff3433493a95b24c364e6056f92025-01-05T12:40:42ZengNature PortfolioNature Communications2041-17232025-01-0116111510.1038/s41467-024-54669-1Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male miceCheukyau Luk0Katherine I. Bridge1Nele Warmke2Katie J. Simmons3Michael Drozd4Amy Moran5Amanda D. V. MacCannell6Chew W. Cheng7Sam Straw8Jason L. Scragg9Jessica Smith10Claire H. Ozber11Chloe G. Wilkinson12Anna Skromna13Natallia Makava14Hiran A. Prag15T. Simon Futers16Oliver I. Brown17Alexander-Francisco Bruns18Andrew MN Walker19Nicole T. Watt20Romana Mughal21Kathryn J. Griffin22Nadira Y. Yuldasheva23Sunti Limumpornpetch24Hema Viswambharan25Piruthivi Sukumar26David J. Beech27Antonio Vidal-Puig28Klaus K. Witte29Michael P. Murphy30Richard C. Hartley31Stephen B. Wheatcroft32Richard M. Cubbon33Lee D. Roberts34Mark T. Kearney35Natalie J. Haywood36Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical CampusLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsUniversity of Cambridge Metabolic Research LaboratoriesLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical CampusSchool of Chemistry, University of GlasgowLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsLeeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of LeedsAbstract During recent decades, changes in lifestyle have led to widespread nutritional obesity and its related complications. Remodelling adipose tissue as a therapeutic goal for obesity and its complications has attracted much attention and continues to be actively explored. The endothelium lines all blood vessels and is close to all cells, including adipocytes. The endothelium has been suggested to act as a paracrine organ. We explore the role of endothelial insulin-like growth factor-1 receptor (IGF-1R), as a paracrine modulator of white adipose phenotype. We show that a reduction in endothelial IGF-1R expression in the presence of high-fat feeding in male mice leads to depot-specific beneficial white adipose tissue remodelling, increases whole-body energy expenditure and enhances insulin sensitivity via a non-cell-autonomous paracrine mechanism. We demonstrate that increased endothelial malonate may be contributory and that malonate prodrugs have potentially therapeutically relevant properties in the treatment of obesity-related metabolic disease.https://doi.org/10.1038/s41467-024-54669-1 |
| spellingShingle | Cheukyau Luk Katherine I. Bridge Nele Warmke Katie J. Simmons Michael Drozd Amy Moran Amanda D. V. MacCannell Chew W. Cheng Sam Straw Jason L. Scragg Jessica Smith Claire H. Ozber Chloe G. Wilkinson Anna Skromna Natallia Makava Hiran A. Prag T. Simon Futers Oliver I. Brown Alexander-Francisco Bruns Andrew MN Walker Nicole T. Watt Romana Mughal Kathryn J. Griffin Nadira Y. Yuldasheva Sunti Limumpornpetch Hema Viswambharan Piruthivi Sukumar David J. Beech Antonio Vidal-Puig Klaus K. Witte Michael P. Murphy Richard C. Hartley Stephen B. Wheatcroft Richard M. Cubbon Lee D. Roberts Mark T. Kearney Natalie J. Haywood Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice Nature Communications |
| title | Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice |
| title_full | Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice |
| title_fullStr | Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice |
| title_full_unstemmed | Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice |
| title_short | Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice |
| title_sort | paracrine role of endothelial igf 1 receptor in depot specific adipose tissue adaptation in male mice |
| url | https://doi.org/10.1038/s41467-024-54669-1 |
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