title: Mesenteric Lymphatic-Perilymphatic Adipose Crosstalk: Role in Alcohol-Induced Perilymphatic Adipose Tissue Inflammation.
abstract: BACKGROUND
  The digestive tract lymphatics transport approximately two-thirds of all lymph produced in the body and have a key role in mucosal immunity through their contribution to antigen transport and immune cell trafficking. Mesenteric lymphatic pumping function integrity is critical for maintaining homeostasis and lipid transport. We previously demonstrated that acute alcohol intoxication (AAI) increases mesenteric lymphatic amplitude of contraction and ejection fraction, enhancing the ability of the lymphatic vessels to pump lymph. AAI has been shown to disrupt intestinal barrier integrity, which would be expected to increase the endotoxin content of mesenteric lymph. In this study, we tested the prediction that AAI increases lymphatic permeability directly affecting perilymphatic adipose tissue (PLAT) milieu.
  
  
  METHODS
  Male Sprague Dawley rats received an intragastric infusion of 2.5 g/kg of alcohol. Isovolumic administration of water (vehicle) served as control. PLAT was isolated for the determination of Evans Blue extravasation (permeability), cytokine content, and immunohistochemistry for inflammatory cell infiltration at 30 minutes and 24 hours after alcohol administration.
  
  
  RESULTS
  PLAT isolated from AAI animals had greater Evans Blue concentrations and cytokine expression (24 hours post-AAI) and mast cell and neutrophil density than that isolated from controls. AAI resulted in significantly higher plasma lipopolysaccharide (endotoxin) levels, lower plasma adiponectin levels (at 30 minutes), and unchanged plasma visfatin levels.
  
  
  CONCLUSIONS
  The data indicate that AAI induces mesenteric lymphatic hyperpermeability, promotes PLAT inflammatory milieu and disrupts the systemic adipokine profile. These findings suggest an association between alcohol-induced lymphatic hyperpermeability and early manifestations of metabolic dysfunction as a result of alcohol abuse. We propose that crosstalk between lymph and PLAT results in adipose inflammation and adipokine dysregulation during AAI.
authors.affiliation: Department of Physiology, Alcohol and Drug Abuse Center of Excellence, LSUHSC, New Orleans, Louisiana.
authors.forename: Flavia M
authors.identifier: http://orcid.org/0000-0002-8287-2261
authors.initials: FM
authors.lastname: Souza-Smith
authors.affiliation: Department of Physiology, Alcohol and Drug Abuse Center of Excellence, LSUHSC, New Orleans, Louisiana.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Siggins
authors.affiliation: Department of Physiology, Alcohol and Drug Abuse Center of Excellence, LSUHSC, New Orleans, Louisiana.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Molina
mesh_terms: D054392:Adipokines / Q000096:biosynthesis; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000435:Alcoholic Intoxication / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D042601:Lymphatic Vessels / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008643:Mesentery / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D054392:Adipokines; D000431:Ethanol
keywords: Adipokine; Endotoxin; Ethanol; Lipopolysaccharide; Lymphatic Permeability