title: Increased adipose tissue secretion of Fetuin-A, lipopolysaccharide-binding protein and high-mobility group box protein 1 in metabolic syndrome.
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.
  
  
  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.
authors.affiliation: Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology, Division of Endocrinology, Diabetes and Metabolism, University of California Davis Medical Center, Sacramento, CA, USA; Medical Services, VA Medical Center, Mather, CA, USA. Electronic address: ishwarlal.jialal@ucdmc.ucdavis.edu.
authors.forename: Ishwarlal
authors.initials: I
authors.lastname: Jialal
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Devaraj
authors.affiliation: Department of Nutrition, University of California Davis, Davis, CA, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Bettaieb
authors.affiliation: Department of Nutrition, University of California Davis, Davis, CA, USA.
authors.forename: Fawaz
authors.initials: F
authors.lastname: Haj
authors.affiliation: Department of Clinical Sciences, Division of Biostatistics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Beverley
authors.initials: B
authors.lastname: Adams-Huet
mesh_terms: D041721:3T3-L1 Cells; D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis; D050154:Adiposity; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D024243:HMGB1 Protein / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D024821:Metabolic Syndrome / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000097:blood; D051197:Toll-Like Receptor 4 / Q000097:blood; D015854:Up-Regulation; D055815:Young Adult; D060749:alpha-2-HS-Glycoprotein / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D002352:Carrier Proteins; D024243:HMGB1 Protein; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D060749:alpha-2-HS-Glycoprotein; D000099231:Lipopolysaccharide-Binding Protein; C556354:AHSG protein, human; C556357:Ahsg protein, mouse; C585491:HMGB1 protein, human; C582808:HMGB1 protein, mouse; C495342:TLR2 protein, human; C495345:TLR4 protein, human
keywords: Adipose tissue; Fetuin A; Lipopolysaccharide binding protein; Metabolic syndrome; TLR