@article{065d9596e7404296899190830bb7dcf5,
title = "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 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.",
keywords = "Adipose Tissue, Phenotype, Endothelial Cells",
author = "Cheukyau Luk and Bridge, {Katherine I.} and Nele Warmke and Simmons, {Katie J.} and Michael Drozd and Amy Moran and MacCannell, {Amanda D.V.} and Cheng, {Chew W.} and Sam Straw and Scragg, {Jason L.} and Jessica Smith and Ozber, {Claire H.} and Wilkinson, {Chloe G.} and Anna Skromna and Natallia Makava and Prag, {Hiran A.} and {Simon Futers}, T. and Brown, {Oliver I.} and Bruns, {Alexander Francisco} and Walker, {Andrew M.N.} and Watt, {Nicole T.} and Romana Mughal and Griffin, {Kathryn J.} and Yuldasheva, {Nadira Y.} and Sunti Limumpornpetch and Hema Viswambharan and Piruthivi Sukumar and Beech, {David J.} and Antonio Vidal-Puig and Witte, {Klaus K.} and Murphy, {Michael P.} and Hartley, {Richard C.} and Wheatcroft, {Stephen B.} and Cubbon, {Richard M.} and Roberts, {Lee D.} and Kearney, {Mark T.} and Haywood, {Natalie J.}",
note = "Funding Information: We would like to acknowledge the histology service from the Division of Pathology and Data Analytics, Colorectal Pathology Trials, University of Leeds, for sectioning and staining adipose and liver samples. The Faculty of Biological Sciences, University of Leeds, Bioimaging Facility has received equipment grants from the Wellcome Trust to purchase confocal microscopes used in this project. M.T.K. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. N.J.H. was funded by a British Heart Foundation Project Grant (PG/18/82/34120) and a and a small grant from the Society ofor Endocrinology. C.L. was funded by a British Heart Foundation PhD studentship (FS/19/59/34896) and a small grant from the Society for Endocrinology. M.D. was funded by a British Heart Foundation Clinical Research Training fellowship (FS/18/44/33792). N.T.W. was funded by a British Heart Foundation Project Grant (PG/14/54/30939). L.D.R. was funded by a Diabetes UK RD Lawrence Fellowship (16/0005382), the Biotechnology and Biological Sciences Research Council (BB/R013500/1) and the Medical Research Council (MR/X009734/1). S.S. was funded by a British Heart Foundation Clinical Research Training Fellowship (FS/CRTF/20/24071). C.H.O. and R.M.C. were funded by British Heart Foundation Clinical Intermediate Fellowships (FS/12/80/29821). A.S. was funded by a British Heart foundation Programme grant (RG/15/7/31521). M.T.K. holds a British Heart Foundation Chair in Cardiovascular and Diabetes research, which also funded NM and KJS (CH/13/1/30086). Work in the MPM lab was supported by the Medical Research Council UK (MC_UU_00028/4) and by a Wellcome Trust Investigator award (220257/Z/20/Z) to MPM. Synthesis in RH\u2019s lab was supported by a Wellcome Trust Investigator award (110158/Z/15/Z). Funding Information: We would like to acknowledge the histology service from the Division of Pathology and Data Analytics, Colorectal Pathology Trials, University of Leeds, for sectioning and staining adipose and liver samples. The Faculty of Biological Sciences, University of Leeds, Bioimaging Facility has received equipment grants from the Wellcome Trust to purchase confocal microscopes used in this project. M.T.K. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. N.J.H. was funded by a British Heart Foundation Project Grant (PG/18/82/34120)\u00A0and a\u00A0and a small grant from the Society ofor Endocrinology. C.L. was funded by a British Heart Foundation PhD studentship (FS/19/59/34896) and a small grant from the Society for Endocrinology. M.D. was funded by a British Heart Foundation Clinical Research Training fellowship (FS/18/44/33792). N.T.W. was funded by a British Heart Foundation Project Grant (PG/14/54/30939). L.D.R. was funded by a Diabetes UK RD Lawrence Fellowship (16/0005382), the Biotechnology and Biological Sciences Research Council (BB/R013500/1) and the Medical Research Council (MR/X009734/1). S.S. was funded by a British Heart Foundation Clinical Research Training Fellowship (FS/CRTF/20/24071). C.H.O. and R.M.C. were funded by British Heart Foundation Clinical Intermediate Fellowships (FS/12/80/29821). A.S. was funded by a British Heart foundation Programme grant (RG/15/7/31521). M.T.K. holds a British Heart Foundation Chair in Cardiovascular and Diabetes research, which also funded NM and KJS (CH /13/1/30086). Work in the MPM lab was supported by the Medical Research Council UK (MC_UU_00028/4) and by a Wellcome Trust Investigator award (220257/Z/20/Z) to MPM. Synthesis in RH\u2019s lab was supported by a Wellcome Trust Investigator award (110158/Z/15/Z). Publisher Copyright: {\textcopyright} The Author(s) 2024.",
year = "2025",
month = jan,
day = "2",
doi = "10.1038/s41467-024-54669-1",
language = "English",
volume = "16",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
