A role for adipocyte-derived lipopolysaccharide-binding protein in inflammation- and obesity-associated adipose tissue dysfunction
Por:
Moreno-Navarrete, JM, Escote, X, Ortega, F, Serino, M, Campbell, M, Michalski, MC, Laville, M, Xifra, G, Luche, E, Domingo, P, Sabater, M, Pardo, G, Waget, A, Salvador, J, Giralt, M, Rodriguez-Hermosa, JI, Camps, M, Kolditz, CI, Viguerie, N, Galitzky, J, Decaunes, P, Ricart, W, Fruhbeck, G, Villarroya, F, Mingrone, G, Langin, D, Zorzano, A, Vidal, H, Vendrell, J, Burcelin, R, Vidal-Puig, A, Fernandez-Real, JM
Publicada:
1 nov 2013
Resumen:
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.
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)gamma agonist were explored. Functional in vitro and ex vivo experiments were also performed.
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 PPAR gamma agonist. Inflammatory agents such as LPS and TNF-alpha 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.
Collectively, these findings suggest that LBP might have an essential role in inflammation- and obesity-associated AT dysfunction.
Filiaciones:
Moreno-Navarrete, JM:
Hosp Univ Dr Josep Trueta, Dept Diabet Endocrinol & Nutr, Inst Invest Biomed Girona IdIBGi, Girona 17007, Spain
Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Barcelona, Spain
Escote, X:
Univ Rovira & Virgili, IISPV, Hosp Joan 23, Dept Endocrinol, E-43007 Tarragona, Spain
Ctr Invest Biomed Red Diabet & Enfermedades Metab, Barcelona, Spain
Ortega, F:
Hosp Univ Dr Josep Trueta, Dept Diabet Endocrinol & Nutr, Inst Invest Biomed Girona IdIBGi, Girona 17007, Spain
Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Barcelona, Spain
Serino, M:
Univ Toulouse 3, INSERM, Inst Malad Metabol & Cardiovasc, F-31062 Toulouse, France
Campbell, M:
Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Dept Clin Biochem,Metab Res Labs, Cambridge CB2 2QQ, England
Michalski, MC:
INSERM, U1060, CarMeN Lab, Oullins, France
Laville, M:
INSERM, U1060, CarMeN Lab, Oullins, France
Xifra, G:
Hosp Univ Dr Josep Trueta, Dept Diabet Endocrinol & Nutr, Inst Invest Biomed Girona IdIBGi, Girona 17007, Spain
Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Barcelona, Spain
Luche, E:
Univ Toulouse 3, INSERM, Inst Malad Metabol & Cardiovasc, F-31062 Toulouse, France
Domingo, P:
Hosp Santa Creu & Sant Pau, Dept Infect Dis, Barcelona, Spain
Sabater, M:
Hosp Univ Dr Josep Trueta, Dept Diabet Endocrinol & Nutr, Inst Invest Biomed Girona IdIBGi, Girona 17007, Spain
Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Barcelona, Spain
Pardo, G:
Hosp Univ Dr Josep Trueta, Dept Diabet Endocrinol & Nutr, Inst Invest Biomed Girona IdIBGi, Girona 17007, Spain
Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Barcelona, Spain
Waget, A:
Univ Toulouse 3, INSERM, Inst Malad Metabol & Cardiovasc, F-31062 Toulouse, France
Salvador, J:
Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Barcelona, Spain
Clin Univ Navarra, Dept Endocrinol, Pamplona, Spain
Clin Univ Navarra, Metab Res Lab, Pamplona, Spain
Giralt, M:
Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Barcelona, Spain
Univ Barcelona IBUB, Inst Biomed, Dept Biochem & Mol Biol, Barcelona, Spain
Rodriguez-Hermosa, JI:
IdIBGi, Dept Surg, Girona, Spain
Camps, M:
Univ Barcelona, Fac Biol, Dept Bioquim & Biol Mol, Barcelona, Spain
Kolditz, CI:
Univ Toulouse 3, INSERM, Inst Malad Metabol & Cardiovasc, F-31062 Toulouse, France
Viguerie, N:
Univ Toulouse 3, INSERM, Inst Malad Metabol & Cardiovasc, F-31062 Toulouse, France
Galitzky, J:
Univ Toulouse 3, INSERM, Inst Malad Metabol & Cardiovasc, F-31062 Toulouse, France
Decaunes, P:
Univ Toulouse 3, INSERM, Inst Malad Metabol & Cardiovasc, F-31062 Toulouse, France
Ricart, W:
Hosp Univ Dr Josep Trueta, Dept Diabet Endocrinol & Nutr, Inst Invest Biomed Girona IdIBGi, Girona 17007, Spain
Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Barcelona, Spain
Fruhbeck, G:
Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Barcelona, Spain
Clin Univ Navarra, Dept Endocrinol, Pamplona, Spain
Clin Univ Navarra, Metab Res Lab, Pamplona, Spain
Villarroya, F:
Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Barcelona, Spain
Univ Barcelona IBUB, Inst Biomed, Dept Biochem & Mol Biol, Barcelona, Spain
Mingrone, G:
Univ Cattolica Sacro Cuore, Dept Internal Med, Rome, Italy
Langin, D:
Univ Toulouse 3, INSERM, Inst Malad Metabol & Cardiovasc, F-31062 Toulouse, France
Zorzano, A:
Ctr Invest Biomed Red Diabet & Enfermedades Metab, Barcelona, Spain
Univ Barcelona, Fac Biol, Dept Bioquim & Biol Mol, Barcelona, Spain
Inst Res Biomed IRB Barcelona, Barcelona, Spain
Vidal, H:
INSERM, U1060, CarMeN Lab, Oullins, France
Vendrell, J:
Univ Rovira & Virgili, IISPV, Hosp Joan 23, Dept Endocrinol, E-43007 Tarragona, Spain
Ctr Invest Biomed Red Diabet & Enfermedades Metab, Barcelona, Spain
Burcelin, R:
Univ Toulouse 3, INSERM, Inst Malad Metabol & Cardiovasc, F-31062 Toulouse, France
Vidal-Puig, A:
Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Dept Clin Biochem,Metab Res Labs, Cambridge CB2 2QQ, England
Fernandez-Real, JM:
Hosp Univ Dr Josep Trueta, Dept Diabet Endocrinol & Nutr, Inst Invest Biomed Girona IdIBGi, Girona 17007, Spain
Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Barcelona, Spain
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