Innate immunity modulates adipokines in humans.
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.
Anderson
Paul D
PD
Cardiovascular Institute, University of Pennsylvania Medical Center, Philadelphia, PA 19104-6160, USA.
Mehta
Nehal N
NN
Wolfe
Megan L
ML
Hinkle
Christine C
CC
Pruscino
Leticia
L
Comiskey
Lynne L
LL
Tabita-Martinez
Jennifer
J
Sellers
Kimberly F
KF
Rickels
Michael R
MR
Ahima
Rexford S
RS
Reilly
Muredach P
MP
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
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