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TNF-α stimulates endothelial palmitic acid transcytosis and promotes insulin resistance

Persistent elevation of plasma TNF-α is a marker of low grade systemic inflammation. Palmitic acid (PA) is the most abundant type of saturated fatty acid in human body. PA is bound with albumin in plasma and could not pass through endothelial barrier freely. Albumin-bound PA has to be transported ac...

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Autores principales: Li, Wenjing, Yang, Xiaoyan, Zheng, Tao, Xing, Shasha, Wu, Yaogong, Bian, Fang, Wu, Guangjie, Li, Ye, Li, Juyi, Bai, Xiangli, Wu, Dan, Jia, Xiong, Wang, Ling, Zhu, Lin, Jin, Si
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356338/
https://www.ncbi.nlm.nih.gov/pubmed/28304381
http://dx.doi.org/10.1038/srep44659
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author Li, Wenjing
Yang, Xiaoyan
Zheng, Tao
Xing, Shasha
Wu, Yaogong
Bian, Fang
Wu, Guangjie
Li, Ye
Li, Juyi
Bai, Xiangli
Wu, Dan
Jia, Xiong
Wang, Ling
Zhu, Lin
Jin, Si
author_facet Li, Wenjing
Yang, Xiaoyan
Zheng, Tao
Xing, Shasha
Wu, Yaogong
Bian, Fang
Wu, Guangjie
Li, Ye
Li, Juyi
Bai, Xiangli
Wu, Dan
Jia, Xiong
Wang, Ling
Zhu, Lin
Jin, Si
author_sort Li, Wenjing
collection PubMed
description Persistent elevation of plasma TNF-α is a marker of low grade systemic inflammation. Palmitic acid (PA) is the most abundant type of saturated fatty acid in human body. PA is bound with albumin in plasma and could not pass through endothelial barrier freely. Albumin-bound PA has to be transported across monolayer endothelial cells through intracellular transcytosis, but not intercellular diffusion. In the present study, we discovered that TNF-α might stimulate PA transcytosis across cardiac microvascular endothelial cells, which further impaired the insulin-stimulated glucose uptake by cardiomyocytes and promoted insulin resistance. In this process, TNF-α-stimulated endothelial autophagy and NF-κB signaling crosstalk with each other and orchestrate the whole event, ultimately result in increased expression of fatty acid transporter protein 4 (FATP4) in endothelial cells and mediate the increased PA transcytosis across microvascular endothelial cells. Hopefully the present study discovered a novel missing link between low grade systemic inflammation and insulin resistance.
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spelling pubmed-53563382017-03-22 TNF-α stimulates endothelial palmitic acid transcytosis and promotes insulin resistance Li, Wenjing Yang, Xiaoyan Zheng, Tao Xing, Shasha Wu, Yaogong Bian, Fang Wu, Guangjie Li, Ye Li, Juyi Bai, Xiangli Wu, Dan Jia, Xiong Wang, Ling Zhu, Lin Jin, Si Sci Rep Article Persistent elevation of plasma TNF-α is a marker of low grade systemic inflammation. Palmitic acid (PA) is the most abundant type of saturated fatty acid in human body. PA is bound with albumin in plasma and could not pass through endothelial barrier freely. Albumin-bound PA has to be transported across monolayer endothelial cells through intracellular transcytosis, but not intercellular diffusion. In the present study, we discovered that TNF-α might stimulate PA transcytosis across cardiac microvascular endothelial cells, which further impaired the insulin-stimulated glucose uptake by cardiomyocytes and promoted insulin resistance. In this process, TNF-α-stimulated endothelial autophagy and NF-κB signaling crosstalk with each other and orchestrate the whole event, ultimately result in increased expression of fatty acid transporter protein 4 (FATP4) in endothelial cells and mediate the increased PA transcytosis across microvascular endothelial cells. Hopefully the present study discovered a novel missing link between low grade systemic inflammation and insulin resistance. Nature Publishing Group 2017-03-17 /pmc/articles/PMC5356338/ /pubmed/28304381 http://dx.doi.org/10.1038/srep44659 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Li, Wenjing
Yang, Xiaoyan
Zheng, Tao
Xing, Shasha
Wu, Yaogong
Bian, Fang
Wu, Guangjie
Li, Ye
Li, Juyi
Bai, Xiangli
Wu, Dan
Jia, Xiong
Wang, Ling
Zhu, Lin
Jin, Si
TNF-α stimulates endothelial palmitic acid transcytosis and promotes insulin resistance
title TNF-α stimulates endothelial palmitic acid transcytosis and promotes insulin resistance
title_full TNF-α stimulates endothelial palmitic acid transcytosis and promotes insulin resistance
title_fullStr TNF-α stimulates endothelial palmitic acid transcytosis and promotes insulin resistance
title_full_unstemmed TNF-α stimulates endothelial palmitic acid transcytosis and promotes insulin resistance
title_short TNF-α stimulates endothelial palmitic acid transcytosis and promotes insulin resistance
title_sort tnf-α stimulates endothelial palmitic acid transcytosis and promotes insulin resistance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356338/
https://www.ncbi.nlm.nih.gov/pubmed/28304381
http://dx.doi.org/10.1038/srep44659
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