Inhibition of Inflammation and iNOS Improves Lymphatic Function in Obesity Academic Article uri icon


MeSH Major

  • Inflammation
  • Lymphatic Vessels
  • Nitric Oxide Synthase Type II
  • Obesity


  • Although recent studies have shown that obesity decreases lymphatic function, the cellular mechanisms regulating this response remain unknown. In the current study, we show that obesity results in perilymphatic accumulation of inflammatory cells and that local inhibition of this response with topical tacrolimus, an inhibitor of T cell differentiation, increases lymphatic vessel density, decreases perilymphatic iNOS expression, increases lymphatic vessel pumping frequency, and restores lymphatic clearance of interstitial fluid to normal levels. Although treatment of obese mice with 1400W, a selective inhibitor of iNOS, also improved lymphatic collecting vessel contractile function, it did not completely reverse lymphatic defects. Mice deficient in CD4(+) cells fed a high fat diet also gained weight relative to controls but were protected from lymphatic dysfunction. Taken together, our findings suggest that obesity-mediated lymphatic dysfunction is regulated by perilymphatic accumulation of inflammatory cells and that T cell inflammatory responses are necessary to initiate this effect.

publication date

  • January 22, 2016



  • Academic Article



  • eng

PubMed Central ID

  • PMC4726274

Digital Object Identifier (DOI)

  • 10.1038/srep19817

PubMed ID

  • 26796537

Additional Document Info

start page

  • 19817


  • 6