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Diabetologia. 2015 Oct;58(10):2424-34. doi: 10.1007/s00125-015-3692-7. Epub 2015 Jul 23.

Lipopolysaccharide binding protein is an adipokine involved in the resilience of the mouse adipocyte to inflammation.

Author information

1
Section of Diabetes, Endocrinology and Nutrition, Hospital of Girona 'Dr Josep Trueta', Carretera de França s/n, 17007, Girona, Spain.
2
Institut d'Investigació Biomèdica de Girona (IdIBGi), Girona, Spain.
3
Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Spain.
4
Department of Endocrinology, Hospital Joan XXIII, Rovira i Virgili University, Tarragona, Spain.
5
Institut d'Investigació Sanitaria Pere Virgili (IISPV), Tarragona, Spain.
6
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
7
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
8
Institute for Research in Biomedicine (IRB), Barcelona, Spain.
9
Department of Clinical Biochemistry, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
10
Section of Diabetes, Endocrinology and Nutrition, Hospital of Girona 'Dr Josep Trueta', Carretera de França s/n, 17007, Girona, Spain. jmfreal@idibgi.org.
11
Institut d'Investigació Biomèdica de Girona (IdIBGi), Girona, Spain. jmfreal@idibgi.org.
12
Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Spain, . jmfreal@idibgi.org.

Abstract

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 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/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.

KEYWORDS:

Adipogenesis; Inflammation; LPS; Lipopolysaccharide binding protein; Palmitate; TLR4

PMID:
26201685
DOI:
10.1007/s00125-015-3692-7
[Indexed for MEDLINE]

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