Adipose tissue secretes a wide range of hormones named adipokines, and these may play a role in obesity-related inflammation. Adiponectin is an exceptional adipokine because low plasma concentrations are associated with obesity, type 2 diabetes and cardio-vascular diseases. It has been observed that plasma adiponectin concentrations are elevated during inflammatory conditions like preeclampsia and arthritis.

Nuclear factor-B (NF-B) is an essential transcription factor for expression of inflammation-related proteins. We have used U937 cells stably transfected to express luciferase under the control of NF-B to examine if adiponectin may modulate NF-B activity. Physiological concentrations of native adiponectin induced NF-B activity. This effect was relatively strong compared with proinflammatory adipokines like leptin, resistin, and IL-6. The enhanced NF-B activity was attributed to the high molecular weight (HMW) adiponectin isoforms. NF-B was not activated by mutated adiponectin that is unable to form HMW complexes. Furthermore, the C-terminal fragment, globular adiponectin, markedly increased NF-B reporter activity, cytokine release and mRNA expression of inflammation marker genes, at higher levels than stimulation with TNF- and lipopolysaccharide (LPS). NF-B activation by globular adiponectin was not affected by antibody inhibition of toll-like receptor 4 (TRL4) or TNF receptors (TNFR)-1 and -2, but was attenuated by inhibitors of p38 MAPK, phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC). Analyses of the p65 subunit of NF-B in different leukocyte cell lines, showed activation of two monocytic cell lines (U937 and THP-1) by native and globular adiponectin. Our results indicate that adiponectin has proinflammatory properties in monocytic cells.