Lipopolysaccharide inhibits the expression of resistin in adipocytes

    1. Weizhen Zhang1,4
    1. 1Department of Physiology and Pathophysiology, Peking University Health Science Center; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China
      2Department of Pathology, Central Hospital of Zibo, Zibo 255000, China
      3Division of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada
      4Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA
    1. Correspondence should be addressed to W Zhang or Y Li, Emails: weizhenzhang{at} or yinli{at}


    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.

    • Revision received 5 August 2013
    • Accepted 22 August 2013
    • Made available online as an Accepted Preprint 22 August 2013
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