title: A role for adipocyte-derived lipopolysaccharide-binding protein in inflammation- and obesity-associated adipose tissue dysfunction.
abstract: OBJECTIVE
  Circulating lipopolysaccharide-binding protein (LBP) is an acute-phase reactant known to be increased in obesity. We hypothesised that LBP is produced by adipose tissue (AT) in association with obesity.
  
  
  METHODS
  LBP mRNA and LBP protein levels were analysed in AT from three cross-sectional (n = 210, n = 144 and n = 28) and three longitudinal (n = 8, n = 25, n = 20) human cohorts; in AT from genetically manipulated mice; in isolated adipocytes; and in human and murine cell lines. The effects of a high-fat diet and exposure to lipopolysaccharide (LPS) and peroxisome proliferator-activated receptor (PPAR)γ agonist were explored. Functional in vitro and ex vivo experiments were also performed.
  
  
  RESULTS
  LBP synthesis and release was demonstrated to increase with adipocyte differentiation in human and mouse AT, isolated adipocytes and human and mouse cell lines (Simpson-Golabi-Behmel syndrome [SGBS], human multipotent adipose-derived stem [hMAD] and 3T3-L1 cells). AT LBP expression was robustly associated with inflammatory markers and increased with metabolic deterioration and insulin resistance in two independent cross-sectional human cohorts. AT LBP also increased longitudinally with weight gain and excessive fat accretion in both humans and mice, and decreased with weight loss (in two other independent cohorts), in humans with acquired lipodystrophy, and after ex vivo exposure to PPARγ agonist. Inflammatory agents such as LPS and TNF-α led to increased AT LBP expression in vivo in mice and in vitro, while this effect was prevented in Cd14-knockout mice. Functionally, LBP knockdown using short hairpin (sh)RNA or anti-LBP antibody led to increases in markers of adipogenesis and decreased adipocyte inflammation in human adipocytes.
  
  
  CONCLUSIONS
  Collectively, these findings suggest that LBP might have an essential role in inflammation- and obesity-associated AT dysfunction.
authors: Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), Hospital Universitari 'Dr Josep Trueta', Carretera de França s/n, 17007, Girona, Spain.
authors: José María
authors: JM
authors: Moreno-Navarrete
authors: Xavier
authors: X
authors: Escoté
authors: Francisco
authors: F
authors: Ortega
authors: Matteo
authors: M
authors: Serino
authors: Mark
authors: M
authors: Campbell
authors: Marie-Caroline
authors: MC
authors: Michalski
authors: Martine
authors: M
authors: Laville
authors: Gemma
authors: G
authors: Xifra
authors: Elodie
authors: E
authors: Luche
authors: Pere
authors: P
authors: Domingo
authors: Mónica
authors: M
authors: Sabater
authors: Gerard
authors: G
authors: Pardo
authors: Aurelie
authors: A
authors: Waget
authors: Javier
authors: J
authors: Salvador
authors: Marta
authors: M
authors: Giralt
authors: Jose I
authors: JI
authors: Rodriguez-Hermosa
authors: Marta
authors: M
authors: Camps
authors: Catherine I
authors: CI
authors: Kolditz
authors: Nathalie
authors: N
authors: Viguerie
authors: Jean
authors: J
authors: Galitzky
authors: Pauline
authors: P
authors: Decaunes
authors: Wifredo
authors: W
authors: Ricart
authors: Gema
authors: G
authors: Frühbeck
authors: Francesc
authors: F
authors: Villarroya
authors: Geltrude
authors: G
authors: Mingrone
authors: Dominique
authors: D
authors: Langin
authors: Antonio
authors: A
authors: Zorzano
authors: Hubert
authors: H
authors: Vidal
authors: Joan
authors: J
authors: Vendrell
authors: Remy
authors: R
authors: Burcelin
authors: Antonio
authors: A
authors: Vidal-Puig
authors: José Manuel
authors: JM
authors: Fernández-Real
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein
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