PMID- 26201685 OWN - NLM STAT- MEDLINE DCOM- 20160627 LR - 20220129 IS - 1432-0428 (Electronic) IS - 0012-186X (Linking) VI - 58 IP - 10 DP - 2015 Oct TI - Lipopolysaccharide binding protein is an adipokine involved in the resilience of the mouse adipocyte to inflammation. PG - 2424-34 LID - 10.1007/s00125-015-3692-7 [doi] AB - AIMS/HYPOTHESIS: 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 gamma (PPAR-gamma) 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 kappaB (NFkappaB) 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/INTERPRETATION: 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. FAU - Moreno-Navarrete, Jose Maria AU - Moreno-Navarrete JM AD - Section of Diabetes, Endocrinology and Nutrition, Hospital of Girona 'Dr Josep Trueta', Carretera de Franca s/n, 17007, Girona, Spain. AD - Institut d'Investigacio Biomedica de Girona (IdIBGi), Girona, Spain. AD - Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Spain. FAU - Escote, Xavier AU - Escote X AD - Department of Endocrinology, Hospital Joan XXIII, Rovira i Virgili University, Tarragona, Spain. AD - Institut d'Investigacio Sanitaria Pere Virgili (IISPV), Tarragona, Spain. AD - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Spain. FAU - Ortega, Francisco AU - Ortega F AD - Section of Diabetes, Endocrinology and Nutrition, Hospital of Girona 'Dr Josep Trueta', Carretera de Franca s/n, 17007, Girona, Spain. AD - Institut d'Investigacio Biomedica de Girona (IdIBGi), Girona, Spain. AD - Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Spain. FAU - Camps, Marta AU - Camps M AD - Departament de Bioquimica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain. FAU - Ricart, Wifredo AU - Ricart W AD - Section of Diabetes, Endocrinology and Nutrition, Hospital of Girona 'Dr Josep Trueta', Carretera de Franca s/n, 17007, Girona, Spain. AD - Institut d'Investigacio Biomedica de Girona (IdIBGi), Girona, Spain. AD - Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Spain. FAU - Zorzano, Antonio AU - Zorzano A AD - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Spain. AD - Departament de Bioquimica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain. AD - Institute for Research in Biomedicine (IRB), Barcelona, Spain. FAU - Vendrell, Joan AU - Vendrell J AD - Department of Endocrinology, Hospital Joan XXIII, Rovira i Virgili University, Tarragona, Spain. AD - Institut d'Investigacio Sanitaria Pere Virgili (IISPV), Tarragona, Spain. AD - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Spain. FAU - Vidal-Puig, Antonio AU - Vidal-Puig A AD - Department of Clinical Biochemistry, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. FAU - Fernandez-Real, Jose Manuel AU - Fernandez-Real JM AD - Section of Diabetes, Endocrinology and Nutrition, Hospital of Girona 'Dr Josep Trueta', Carretera de Franca s/n, 17007, Girona, Spain. jmfreal@idibgi.org. AD - Institut d'Investigacio Biomedica de Girona (IdIBGi), Girona, Spain. jmfreal@idibgi.org. AD - Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Spain, . jmfreal@idibgi.org. LA - eng GR - RG/12/13/29853/BHF_/British Heart Foundation/United Kingdom GR - DH_/Department of Health/United Kingdom GR - MC_UU_12012/2/MRC_/Medical Research Council/United Kingdom GR - G0802051/MRC_/Medical Research Council/United Kingdom GR - G0400192/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150723 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Acute-Phase Proteins) RN - 0 (Carrier Proteins) RN - 0 (Lipopolysaccharides) RN - 0 (Membrane Glycoproteins) RN - 0 (NF-kappa B) RN - 0 (lipopolysaccharide-binding protein) RN - 2V16EO95H1 (Palmitic Acid) SB - IM MH - 3T3-L1 Cells MH - Acute-Phase Proteins/genetics/*metabolism MH - Adipocytes/drug effects/*metabolism MH - Adipogenesis/drug effects/*genetics MH - Animals MH - Carrier Proteins/genetics/*metabolism MH - Gene Expression MH - Gene Knockdown Techniques MH - Inflammation/genetics/*metabolism MH - Lipopolysaccharides/pharmacology MH - Membrane Glycoproteins/genetics/*metabolism MH - Mice MH - NF-kappa B/metabolism MH - Palmitic Acid/pharmacology MH - Signal Transduction/drug effects/genetics OTO - NOTNLM OT - Adipogenesis OT - Inflammation OT - LPS OT - Lipopolysaccharide binding protein OT - Palmitate OT - TLR4 EDAT- 2015/07/24 06:00 MHDA- 2016/06/28 06:00 CRDT- 2015/07/24 06:00 PHST- 2015/04/09 00:00 [received] PHST- 2015/06/17 00:00 [accepted] PHST- 2015/07/24 06:00 [entrez] PHST- 2015/07/24 06:00 [pubmed] PHST- 2016/06/28 06:00 [medline] AID - 10.1007/s00125-015-3692-7 [pii] AID - 10.1007/s00125-015-3692-7 [doi] PST - ppublish SO - Diabetologia. 2015 Oct;58(10):2424-34. doi: 10.1007/s00125-015-3692-7. Epub 2015 Jul 23.