Obesity but not high-fat diet impairs lymphatic function Journal Article
| Authors: | García Nores, G. D.; Cuzzone, D. A.; Albano, N. J.; Hespe, G. E.; Kataru, R. P.; Torrisi, J. S.; Gardenier, J. C.; Savetsky, I. L.; Aschen, S. Z.; Nitti, M. D.; Mehrara, B. J. |
| Article Title: | Obesity but not high-fat diet impairs lymphatic function |
| Abstract: | Background/Objectives:High-fat diet (HFD)-induced obesity has significant negative effects on lymphatic function, but it remains unclear whether this is a direct effect of HFD or secondary to adipose tissue deposition.Methods:We compared the effects of HFD on obesity-prone and obesity-resistant mice and analyzed lymphatic function in vivo and in vitro.Results:Only obesity-prone mice had impaired lymphatic function, increased perilymphatic inflammation and accumulation of lipid droplets surrounding their lymphatic endothelial cells (LECs). LECs isolated from obesity-prone mice, in contrast to obesity-resistant animals, had decreased expression of VEGFR-3 and Prox1. Exposure of LECs to a long-chain free fatty acid increased cellular apoptosis and decreased VEGFR-3 expression, while inhibition of intracellular inhibitors of VEGFR-3 signaling pathways increased cellular viability.Conclusions:Collectively, our studies suggest that HFD-induced obesity decreases lymphatic function by increasing perilymphatic inflammation and altering LEC gene expression. Reversal of diminished VEGFR-3 signaling may rescue this phenotype and improve lymphatic function. © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. |
| Keywords: | signal transduction; vasculotropin receptor 3; controlled study; protein expression; unclassified drug; human cell; nonhuman; animal cell; mouse; animal tissue; cell viability; apoptosis; inflammation; protein; obesity; in vivo study; in vitro study; endothelium cell; lymph vessel; lymph vessel endothelium; lipid diet; fat droplet; human; male; priority journal; article; long chain fatty acid; prox1 protein; perilymph |
| Journal Title: | International Journal of Obesity |
| Volume: | 40 |
| Issue: | 10 |
| ISSN: | 0307-0565 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2016-10-01 |
| Start Page: | 1582 |
| End Page: | 1590 |
| Language: | English |
| DOI: | 10.1038/ijo.2016.96 |
| PROVIDER: | scopus |
| PMCID: | PMC5050064 |
| PUBMED: | 27200507 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2016 -- Source: Scopus |
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