"Influence of Obesity, Weight Loss, and Diet on Low Grade Inflammation With Particular Focus on the Macrophage Marker, Soluble-CD163 - a New Predictor of Diabetes.Can s-CD163 Discriminate Between Healthy and Unhealthy Obese Individuals?"

It is recognized that low grade inflammation is a key player in the development of atherosclerosis and insulin resistance (Haslam, James 2005). Circulating levels of inflammatory markers such as high sensitive C-reactive protein (hsCRP) and interleukin (IL)-6 are found to be increased in subjects with cardiovascular disease (CVD) and type 2-diabetes (Dandona, Aljada & Bandyopadhyay 2004). We and others have shown that obesity, and in particular abdominal obesity, is associated with persistent increased level of inflammatory markers (Bruun et al. 2007, Christiansen et al. 2010a) . Thus this low grade of inflammation may represent "the common soil" for the pathogenesis of atherosclerosis and insulin resistance and represent the link between these metabolic disturbances and obesity.

Besides its function as a storage organ, the adipose tissue (AT) exerts a complex role in the organism. In obesity the adipose tissue is infiltrated by an increased amount of macrophages, and particular these macrophages express and release a wide range of hormones and cytokines, collectively called adipokines, which biological functions are shown to include involvement in glucose metabolism, lipid metabolism, adipocyte differentiation, immunity, vasculature and neuron development and eating behavior (Trayhurn, Wood 2004).

Among the adipokines expressed in the AT are pro-inflammatory cytokines as TNFα, IL-6, pro-inflammatory chemokines as IL-8, MCP-1, MIP1α, thrombotic factors as plasminogen inhibitor 1 (PAI-1), and AT specific proteins as adiponectin and leptin.

Hypertrophied adipocytes, as seen in obese subjects and associated with insulin resistance are shown to display a distinct gene expression of inflammatory markers compared to small human adipocytes and it is shown that adipocyte size is an important determinant of adipokine secretion. Moreover an positive association between the grade of obesity and the expression of pro-inflammatory cytokines as TNFα, IL-6, IL-8, has been found whereas and an inverse association between adiponectin and obesity has been reported (Kern et al. 2003, Bruun et al. 2003).In accordance with these observations, we have found the AT expression of MCP-1 was up-regulated in obese subjects (Christiansen, Richelsen & Bruun 2005) whereas the AT expression of adiponectin in obese subjects (mean BMI 40 kg/m2 ) was found down-regulated with 50% as compared to lean subjects (mean BMI 22 kg/m2) (Christiansen et al. 2010b).

Thus, adipose tissue inflammation resulting in dysfunction of the adipose tissue may be the important factor relating obesity to insulin resistance, metabolic syndrome, diabetes, and cardiovascular diseases.