Increased adipose tissue secretion of Fetuin-A, lipopolysaccharide-binding protein and high-mobility group box protein 1 in metabolic syndrome

Ishwarlal Jialal, Sridevi Devaraj, Ahmed Bettaieb, Fawaz Haj, Beverley Adams-Huet

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Objective: Adipose Tissue (AT) dysregulation contributes to the pro-inflammatory state and insulin resistance of Metabolic Syndrome (MetS). We examined AT secretion of the hepatokine, Fetuin-A, LBP, sCD14 and HMGB-1, and toll-like receptor 2 and 4 protein levels in MetS and controls. Design and methods: Secreted levels of Fetuin-A, LBP, HMGB-1 and sCD14 and TLR2 and TLR4 protein in AT of controls and MetS patients were assayed. Also mRNA and protein for Fetuin-A, LBP, sCD14 and HMGB-1 were studied in subcutaneous fat depot of mice and during adipocyte differentiation. Results: Secretion of Fetuin-A, LBP and HMGB-1 from AT were significantly increased in MetS (n=28) compared to controls (n=25), even after adjustment for adiposity. There were no significant differences in sCD14. Both LBP and Fetuin-A correlated significantly with HOMA-IR and increased significantly with increasing features of MetS. There was a significant increase in AT TLR2 and TLR4 protein in MetS compared to controls. Expression of Fetuin-A and LBP were significantly higher in subcutaneous white adipose tissue of HFD fed mice as well as in ob/ob mice compared to C57BL6/J control mice (n=6 per group). Additionally mRNA and protein levels of FetA, LBP and HMGB-1 increased during differentiation of 3T3-L1 adipocytes. Conclusions: We make the novel observation of increased secretion of Fetuin A, LBP and HMGB-1 from AT and hypothesize that these engage TLRs in AT and other tissues contributing to the pro-inflammatory state and insulin resistance of MetS.

Original languageEnglish (US)
Pages (from-to)130-137
Number of pages8
JournalAtherosclerosis
Volume241
Issue number1
DOIs
StatePublished - Jul 1 2015

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Keywords

  • Adipose tissue
  • Fetuin A
  • Lipopolysaccharide binding protein
  • Metabolic syndrome
  • TLR

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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