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Diabetologia
Published in: Diabetologia 11/2013

01-11-2013 | Article

A role for adipocyte-derived lipopolysaccharide-binding protein in inflammation- and obesity-associated adipose tissue dysfunction

Authors: José María Moreno-Navarrete, Xavier Escoté, Francisco Ortega, Matteo Serino, Mark Campbell, Marie-Caroline Michalski, Martine Laville, Gemma Xifra, Elodie Luche, Pere Domingo, Mónica Sabater, Gerard Pardo, Aurelie Waget, Javier Salvador, Marta Giralt, Jose I. Rodriguez-Hermosa, Marta Camps, Catherine I. Kolditz, Nathalie Viguerie, Jean Galitzky, Pauline Decaunes, Wifredo Ricart, Gema Frühbeck, Francesc Villarroya, Geltrude Mingrone, Dominique Langin, Antonio Zorzano, Hubert Vidal, Joan Vendrell, Remy Burcelin, Antonio Vidal-Puig, José Manuel Fernández-Real

Published in: Diabetologia | Issue 11/2013

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Abstract

Aims/hypothesis

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/interpretation

Collectively, these findings suggest that LBP might have an essential role in inflammation- and obesity-associated AT dysfunction.
Appendix
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Metadata
Title
A role for adipocyte-derived lipopolysaccharide-binding protein in inflammation- and obesity-associated adipose tissue dysfunction
Authors
José María Moreno-Navarrete
Xavier Escoté
Francisco Ortega
Matteo Serino
Mark Campbell
Marie-Caroline Michalski
Martine Laville
Gemma Xifra
Elodie Luche
Pere Domingo
Mónica Sabater
Gerard Pardo
Aurelie Waget
Javier Salvador
Marta Giralt
Jose I. Rodriguez-Hermosa
Marta Camps
Catherine I. Kolditz
Nathalie Viguerie
Jean Galitzky
Pauline Decaunes
Wifredo Ricart
Gema Frühbeck
Francesc Villarroya
Geltrude Mingrone
Dominique Langin
Antonio Zorzano
Hubert Vidal
Joan Vendrell
Remy Burcelin
Antonio Vidal-Puig
José Manuel Fernández-Real
Publication date
01-11-2013
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 11/2013
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-013-3015-9

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