title: Lipopolysaccharide binding protein is an adipokine involved in the resilience of the mouse adipocyte to inflammation.
abstract: OBJECTIVE
  Lipopolysaccharide (LPS) binding protein (LBP) is a novel 65 kDa adipokine, linked to adipose tissue (AT) inflammation, obesity and insulin resistance, that inhibits adipocyte differentiation. Here, we investigated the molecular mechanisms behind these detrimental effects on adipogenesis through whole-genome transcriptomics and in vitro experiments.
  
  
  METHODS
  Permanent and transient knockdown (KD) and co-culture experiments were performed in 3T3-L1 and 3T3-F442A cell lines during adipocyte differentiation. Microarray gene expression was performed using Genechip Affymetrix technology and validated by real-time PCR.
  
  
  RESULTS
  LBP KD of 3T3-L1 cells led to a potentiated adipocyte differentiation with a dose-response relationship; genes involved in mitochondrial biogenesis, fatty acid metabolism and peroxisome proliferator-activated receptor γ (PPAR-γ) action were dramatically upregulated in parallel to increased insulin signalling. Cells with LBP KD became refractory to proinflammatory cytokines and other inflammatory stimuli (LPS and palmitate). This phenotype, mediated through disrupted nuclear factor κB (NFκB) signalling, was reversed by a soluble factor present in a co-culture with native cells and by exogenous LBP. Double-silencing of LBP and toll-like receptor 4 (TLR4) again rendered these cells insensitive to co-culture, LBP and inflammatory factors.
  
  
  CONCLUSIONS
  In summary, LBP is a proinflammatory soluble adipokine that acts as a brake for adipogenesis, strengthening the negative effects of palmitate and LPS on adipocyte differentiation.
authors.affiliation: Section of Diabetes, Endocrinology and Nutrition, Hospital of Girona 'Dr Josep Trueta', Carretera de França s/n, 17007, Girona, Spain.|Institut d'Investigació Biomèdica de Girona (IdIBGi), Girona, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Moreno-Navarrete
authors.affiliation: Department of Endocrinology, Hospital Joan XXIII, Rovira i Virgili University, Tarragona, Spain.|Institut d'Investigació Sanitaria Pere Virgili (IISPV), Tarragona, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Escoté
authors.affiliation: Section of Diabetes, Endocrinology and Nutrition, Hospital of Girona 'Dr Josep Trueta', Carretera de França s/n, 17007, Girona, Spain.|Institut d'Investigació Biomèdica de Girona (IdIBGi), Girona, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ortega
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Camps
authors.affiliation: Section of Diabetes, Endocrinology and Nutrition, Hospital of Girona 'Dr Josep Trueta', Carretera de França s/n, 17007, Girona, Spain.|Institut d'Investigació Biomèdica de Girona (IdIBGi), Girona, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Spain.
authors.forename: Wifredo
authors.initials: W
authors.lastname: Ricart
authors.affiliation: Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.|Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.|Institute for Research in Biomedicine (IRB), Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Zorzano
authors.affiliation: Department of Endocrinology, Hospital Joan XXIII, Rovira i Virgili University, Tarragona, Spain.|Institut d'Investigació Sanitaria Pere Virgili (IISPV), Tarragona, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Vendrell
authors.affiliation: Department of Clinical Biochemistry, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Antonio
authors.initials: A
authors.lastname: Vidal-Puig
authors.affiliation: Section of Diabetes, Endocrinology and Nutrition, Hospital of Girona 'Dr Josep Trueta', Carretera de França s/n, 17007, Girona, Spain. jmfreal@idibgi.org.|Institut d'Investigació Biomèdica de Girona (IdIBGi), Girona, Spain. jmfreal@idibgi.org.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Spain, . jmfreal@idibgi.org.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Fernández-Real
mesh_terms: D041721:3T3-L1 Cells; D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D019308:Palmitic Acid; D000099231:Lipopolysaccharide-Binding Protein
keywords: Adipogenesis; Inflammation; LPS; Lipopolysaccharide binding protein; Palmitate; TLR4