title: Lipopolysaccharide inhibits the expression of resistin in adipocytes.
abstract: Resistin is an adipocytokine leading to insulin resistance. Endotoxin/lipopolysaccharide (LPS) has been reported to decrease the expression of resistin mRNA and protein in both lean and db/db obese mice, although the underlying mechanism remains unclear. Several models such as ex vivo culture of adipose tissues, primary rat adipocytes and 3T3-L1 adipocytes were used to further characterize the effect of LPS on the expression of resistin. LPS attenuated both the resistin mRNA and protein in a time- and dose-dependent manner. In the presence of actinomycin D, LPS failed to reduce the half-life of resistin mRNA, suggesting a transcriptional mechanism. The lipid A fraction is crucial for the inhibition of resistin expression induced by LPS. Pharmacological intervention of c-Jun N-terminal kinase (JNK) reversed the inhibitory effect of LPS. LPS down-regulated CCAAT/enhancer-binding protein α (C/EBP-α; CEBPA) and peroxisome proliferator-activated receptor γ (PPAR-γ; PPARG), while activation of C/EBP-α or PPAR-γ by either over-expressing these transcriptional factors or by rosiglitazone, an agonist of PPAR-γ, blocked the inhibitory effect of LPS on resistin. C/EBP homologous protein (CHOP-10; DDIT3) was up-regulated by LPS, while a CHOP-10 antisense oligonucleotide reversed the decrement of resistin protein induced by LPS. Taken together, these results suggest that LPS inhibits resistin expression through a unique signaling pathway involving toll-like receptor 4, JNK, CHOP-10 and C/EBP-α/PPAR-γ.
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China Department of Pathology, Central Hospital of Zibo, Zibo 255000, China Division of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
authors: Xinxin
authors: X
authors: Xiang
authors: Wenjiao
authors: W
authors: An
authors: Changtao
authors: C
authors: Jiang
authors: Jing
authors: J
authors: Zhao
authors: Xian
authors: X
authors: Wang
authors: Guang
authors: G
authors: Sun
authors: Yin
authors: Y
authors: Li
authors: Weizhen
authors: W
authors: Zhang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D005951:Glucose Tolerance Test; D008050:Lipid A / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D052243:Resistin / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D008050:Lipid A; D008070:Lipopolysaccharides; D052243:Resistin; D051197:Toll-Like Receptor 4
keywords: C/EBP-α; CHOP-10; JNK; LPS; PPAR-γ; resistin