title: Obesity but not high-fat diet impairs lymphatic function.
abstract: 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.
  
  
  
  We compared the effects of HFD on obesity-prone and obesity-resistant mice and analyzed lymphatic function in vivo and in vitro.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Plastic and Reconstructive Surgery, The Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: García Nores
authors.affiliation: Division of Plastic and Reconstructive Surgery, The Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Cuzzone
authors.affiliation: Division of Plastic and Reconstructive Surgery, The Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Albano
authors.affiliation: Division of Plastic and Reconstructive Surgery, The Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: G E
authors.initials: GE
authors.lastname: Hespe
authors.affiliation: Division of Plastic and Reconstructive Surgery, The Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Kataru
authors.affiliation: Division of Plastic and Reconstructive Surgery, The Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Torrisi
authors.affiliation: Division of Plastic and Reconstructive Surgery, The Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Gardenier
authors.affiliation: Division of Plastic and Reconstructive Surgery, The Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: I L
authors.initials: IL
authors.lastname: Savetsky
authors.affiliation: Division of Plastic and Reconstructive Surgery, The Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: S Z
authors.initials: SZ
authors.lastname: Aschen
authors.affiliation: Division of Plastic and Reconstructive Surgery, The Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Nitti
authors.affiliation: Division of Plastic and Reconstructive Surgery, The Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Mehrara
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism; D007249:Inflammation; D042601:Lymphatic Vessels / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D040321:Vascular Endothelial Growth Factor Receptor-3