**2.3. Adiponectin**

Adiponectin, also known as ACRP 30 (adipocyte complement related protein of 30kDa), apM1 (adipose most abundant gene transcript 1), AdipQ or GBP28 (gelatin binding protein of 28 kDa) [49-52], is a protein exclusively expressed in differentiated adipocytes and circulates in high levels in the blood [53], presenting greater expression in subcutaneous adipose tissue than in visceral adipose tissue [54]. Unlike other factors secreted by adipose tissue, adiponectin acts as a protective factor for cardiovascular disease and increases insulin sensitivity. It is an approximately 30 kDa polypeptide that shows high homology with collagen VIII and X, and complement component C1q. A proteolytic cleavage product containing the globular domain of adiponectin circulate in physiologically significant levels and has biological activity [53].

Except for cases of severe malnutrition [55] and in neonates [56], there is a strong negative correlation between plasma adiponectin and fat mass [52].

Were identified two adiponectin receptors isoforms (Adipo-R1 and -R2) [57]. This receptors present seven transmembrane domains but are functionally different of receptors coupled to G protein. AdipoR1 is expressed mainly in muscle tissue and has high affinity for globular adiponectin, and low affinity for full-length adiponectin. AdipoR2 has high expression in liver and has intermediate affinity for both isoforms of circulating adiponectin. Thus, it is noted that the biological effects of adiponectin depends not only on circulating levels or the properties of each isoform but also receptor subtype and its expression in each tissue [3].

Adiponectin anti-inflammatory and anti-atherogenic actions occurs through decreased expression of adhesion molecule-1 (via reduced expression of TNF-alpha activity and resistin); decreased macrophage chemotaxis to fat cells formation; and inhibition of inflammatory signaling in endothelial tissue [58]. It increases insulin sensitivity via increased fatty acid oxidation and glucose uptake and utilization in skeletal muscle and adipose tissue; reduction of hepatic glucose release, leading to better control of glucose serum levels, free fatty acids and triglycerides [59]. In rat adipocytes, *in vitro*, the 60% reduction in adiponectin expression increased significantly insulin resistance. The presence of nucleotide polymorphisms in adiponectin caused by genetic or environmental factors (diet rich in fat, for example), can be a determining factor in reducing their insulin sensitizing action [60].

In the liver, adiponectin increases insulin sensitivity by reducing nonesterified fatty acids uptake, increasing fatty acid oxidation and decreasing glucose output. In muscle, adiponectin stimulates glucose metabolism and fatty acid oxidation. In the endothelium, it inhibits monocyte adherence by reducing adhesion molecules; inhibits macrophages transformation and reduces migrating smooth muscle cells proliferation in response to growth factors. Adiponectin also increases nitric oxide production by endothelial cells and stimulates angiogenesis. Taken together, these effects suggest that adiponectin is the only adipokine that present antidiabetic, anti-inflammatory and anti-atherogenic effects [3].
