TY - JOUR
T1 - Innate immunity modulates adipokines in humans
AU - Anderson, Paul D.
AU - Mehta, Nehal N.
AU - Wolfe, Megan L.
AU - Hinkle, Christine C.
AU - Pruscino, Leticia
AU - Comiskey, Lynne L.
AU - Tabita-Martinez, Jennifer
AU - Sellers, Kimberly F.
AU - Rickels, Michael R.
AU - Ahima, Rexford S.
AU - Reilly, Muredach P.
N1 - Funding Information:
Disclosure Statement: M.P.R. has received, within the past 2 yr, research funding from GlaxoSmithKline, Merck & Co., Eli Lilly Inc., and KOS Pharmaceuticals. R.S.A. has served as consultant to Ipsen Pharmaceuticals. N.N.M., K.F.S., and M.R.R. as well as P.D.A. and M.L.W., C.C.H., L.L.C., L.P., and J.T.-M. have no potential conflict of interest.
Funding Information:
The authors appreciate the support for P.D.A. provided by the Sarnoff Cardiovascular Research Foundation's Sarnoff Fellowship Program.
Funding Information:
This work was supported by Grant M01-RR00040 from the National Center for Research Resources/National Institutes of Health (NCRR/NIH) to the University of Pennsylvania General Clinical Research Center, by HL RO1073278 from the NCRR/NIH (to M.P.R.) and the W. W. Smith Charitable Trust (no. H0204) (to M.P.R.), and by the Sarnoff Cardiovascular Research Foundation, formerly the Sarnoff Endowment for Cardiovascular Science, Inc. (to P.D.A.).
PY - 2007/6
Y1 - 2007/6
N2 - Context: 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. Design/Setting: An open-label, placebo-controlled, fixed-sequence clinical study was conducted at a General Clinical Research Center. Patients: There were 20 healthy male (50%) and female volunteers aged 18-40 yr. Intervention: Serial blood sampling and adipose biopsies were performed for 24 h before and after iv bolus endotoxin [lipopolysaccharide (LPS), 3 ng/kg]. Main Outcome Measures: 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.
AB - Context: 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. Design/Setting: An open-label, placebo-controlled, fixed-sequence clinical study was conducted at a General Clinical Research Center. Patients: There were 20 healthy male (50%) and female volunteers aged 18-40 yr. Intervention: Serial blood sampling and adipose biopsies were performed for 24 h before and after iv bolus endotoxin [lipopolysaccharide (LPS), 3 ng/kg]. Main Outcome Measures: 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.
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U2 - 10.1210/jc.2006-2545
DO - 10.1210/jc.2006-2545
M3 - Article
C2 - 17374708
AN - SCOPUS:34347240423
SN - 0021-972X
VL - 92
SP - 2272
EP - 2279
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 6
ER -