Peripheral Factors in the Metabolic Syndrome The Pivotal Role of Adiponectin

• Published in: Annals of the New York Academy of Sciences Vol. 1083; no. 1; pp. 185 - 195
• Main Authors: TSATSANIS, CHRISTOS, ZACHARIOUDAKI, VASSILIKI, ANDROULIDAKI, ARIADNE, DERMITZAKI, ERINI, CHARALAMPOPOULOS, IOANNIS, MINAS, VASSILIS, GRAVANIS, ACHILLE, MARGIORIS, ANDREW N.
• Format: Journal Article
• Language: English
• Published: United States 01.11.2006
• Subjects: Adiponectin - pharmacology; Adiponectin - physiology; Cell Line; Cytokines - biosynthesis; Dose-Response Relationship, Drug; Humans; Inflammation - immunology; Interleukin-1beta - biosynthesis; Interleukin-6 - biosynthesis; Interleukin-8 - biosynthesis; Macrophages - metabolism; Metabolic Syndrome - immunology; Monocytes - metabolism; Obesity - metabolism; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1196/annals.1367.013

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‐1β (IL‐1β), IL‐6, tumor necrosis factor α (TNF‐α), 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‐1β 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‐α, 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.