title: Innate immunity modulates adipokines in humans.
abstract: BACKGROUND
  Chronic inflammation converges in type 2 diabetes and atherosclerosis. Modulation of adipokine signaling by innate immunity in humans is of considerable interest given the role of adipokines in insulin resistance and atherosclerosis.
  
  
  OBJECTIVE
  The aim of the study was to examine effects of low-grade endotoxemia, a model of human inflammation, on adipokines in vivo.
  
  
  METHODS
  An open-label, placebo-controlled, fixed-sequence clinical study was conducted at a General Clinical Research Center.
  
  
  METHODS
  There were 20 healthy male (50%) and female volunteers aged 18-40 yr.
  
  
  METHODS
  Serial blood sampling and adipose biopsies were performed for 24 h before and after iv bolus endotoxin [lipopolysaccharide (LPS), 3 ng/kg].
  
  
  METHODS
  We measured plasma leptin, adiponectin, resistin, soluble leptin receptor, cytokines, insulin, and glucose; distribution of adiponectin among multimeric complexes; whole blood, monocyte and adipose mRNA for adipokines and their receptors.
  
  
  RESULTS
  LPS induced fever, blood, and adipose TNF and IL-6 and increased homeostasis model assessment of insulin resistance. These were associated with increases in plasma leptin (from 4.1 +/- 1.1 to 6.1 +/- 1.9 ng/ml in men; 21.1 +/- 4.4 to 27.4 +/- 4.7 ng/ml in women; P < 0.005), doubling of the leptin:soluble leptin receptor ratio, and marked induction of whole blood resistin mRNA (13.7 +/- 7.3-fold; P < 0.001) and plasma resistin (8.5 +/- 2.75 to 43.2 +/- 15.3 ng/ml; P < 0.001). Although total adiponectin levels and low and high molecular weight adiponectin complexes were unaltered by LPS treatment, whole blood mRNA for adiponectin receptors 1 (49%; P < 0.005) and 2 (65%; P < 0.001) was suppressed.
  
  
  CONCLUSIONS
  Modulation of adipokine signaling may contribute to the insulin resistant, atherogenic state associated with human inflammatory syndromes. Targeting of individual adipokines or their upstream regulation may prove effective in preventing acute and chronic inflammation-related metabolic complications.
authors: Cardiovascular Institute, University of Pennsylvania Medical Center, Philadelphia, PA 19104-6160, USA.
authors: Paul D
authors: PD
authors: Anderson
authors: Nehal N
authors: NN
authors: Mehta
authors: Megan L
authors: ML
authors: Wolfe
authors: Christine C
authors: CC
authors: Hinkle
authors: Leticia
authors: L
authors: Pruscino
authors: Lynne L
authors: LL
authors: Comiskey
authors: Jennifer
authors: J
authors: Tabita-Martinez
authors: Kimberly F
authors: KF
authors: Sellers
authors: Michael R
authors: MR
authors: Rickels
authors: Rexford S
authors: RS
authors: Ahima
authors: Muredach P
authors: MP
authors: Reilly
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000235:genetics; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000235:genetics; D019446:Endotoxemia / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007107:Immune System / Q000276:immunology* / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood / Q000235:genetics; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D036361:Peptide Hormones / Q000097:blood* / Q000235:genetics; D010919:Placebos; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000097:blood / Q000235:genetics; D054411:Receptors, Leptin; D052243:Resistin / Q000097:blood / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin; D020738:Leptin; D008070:Lipopolysaccharides; D036361:Peptide Hormones; D010919:Placebos; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D052243:Resistin