Peripheral factors in the metabolic syndrome: the pivotal role of adiponectin.
Several recently published reports, including ours, suggest that adiponectin is a strong proinflammatory agent. Indeed, exposure of human placenta and adipose tissue to adiponectin induces the production of interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha), and prostaglandin E2 (PGE2). We have previously shown that adiponectin is a powerful inducer of proinflammatory cytokines production by macrophages. The reported anti-inflammatory effect of adiponectin may be due to the induction of macrophage tolerance to further adiponectin exposure or to other proinflammatory stimuli including the Toll-like receptor (TLR) 3 ligand polyI:C and the TLR4 ligand lipopolysaccharide (LPS). We now present additional data supporting the hypothesis that adiponectin is a strong proinflammatory adipokine. More specifically, we demonstrate that adiponectin induces IL-1beta and IL-8 from THP-1 macrophage cell line. The effect of adiponectin is not restricted to differentiated THP-1 macrophages but it is evident at lower levels in undifferentiated THP-1 monocytes promoting TNF-alpha, IL-6, and IL-8 production. Thus, its high levels in the circulation of lean subjects render their macrophages resistant to several proinflammatory stimuli including its own thus acting in effect as an anti-inflammatory agent. Lowering of its high levels, as a consequence of increased body mass index (BMI), renders macrophages sensitive to any proinflammatory insult.
Tsatsanis
Christos
C
Department of Clinical Chemistry-Biochemistry, University of Crete, Heraklion GR-710 03, Crete, Greece.
Zacharioudaki
Vassiliki
V
Androulidaki
Ariadne
A
Dermitzaki
Erini
E
Charalampopoulos
Ioannis
I
Minas
Vassilis
V
Gravanis
Achille
A
Margioris
Andrew N
AN
D052242:Adiponectin / Q000494:pharmacology / Q000502:physiology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism; D024821:Metabolic Syndrome / Q000276:immunology*; D009000:Monocytes / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D052242:Adiponectin; D016207:Cytokines; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha