Obesity is a chronic inflammatory disease as shown by circulaing levels of cytokines and chemokines, as well as the dysregulated expression and production of inflammation-related genes and molecules in the adipose tissue. The importance of the low-grade inflammation is supported by the demonstration that elevated levels of of acute phase reactants and immune mediators are independently associated with increased risk for type 2 diabetes and cardio-vascular disease. A dysregulated adipose organ, in part due to fat cell hypertrophy and the accompanying infiltration of macrophages leads to an activation of inflammatory pathways in the cells with increased gene and protein expression of TNFa, IL-6, IL-8 and MCP-1 as well as a reduced secretion of adiponectin. The accentuated production of cytokines/chemo-kines aggravates differentiation of the preadipocytes leading to local and systemic insulin resistance, including an attenuated antilipolytic effect of insulin on FFA production.

However, the quantitative importance of the inflamed adipose tissue to the serum levels of inflammatory biomarkers remains to be established. To further address this question, we have used the microdialysis technique (linear probe, Plasmaflo OP-02, polyethylene, pore size 0.3mm, membrane length ca 30 mm, Asahi Medical, Tokyo, Japan) for sampling of extracellular proteins in the subcutaneous periumbilical region. In situ microdialysate samples (combined with the Luminex technique), subcutaneous needle biopsies and blood samples were obtained from lean and obese subjects. Our data indicate that several cytokines/chemo-kines mainly act as paracrine/autocrine regulators with a minor "spillover" to the circulating levels.