Lipopolysaccharide binding protein is an adipokine involved in the resilience of the mouse adipocyte to inflammation.
Diabetologia
; 58(10): 2424-34, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-26201685
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Fase Aguda
/
Glicoproteínas de Membrana
/
Proteínas de Transporte
/
Adipócitos
/
Adipogenia
/
Inflamação
Limite:
Animals
Idioma:
En
Revista:
Diabetologia
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Espanha