Actions of Adiponectin

The mechanisms whereby adiponectin exerts its physiological actions are not entirely clear. Apart from its role as an insulin-sensitizing agent, and its implication in metabolic disorders, adiponectin might also be involved in the regulation of inflammatory processes that contribute to atherosclerosis. Because adiponectin and TNF-a are both secreted by adipose tissue, a direct link between these two markers seems conceivable. Indeed, TNF-a has been suggested to be a strong inhibitor of the adiponectin promoter activity (130), whereas adiponectin, in turn, reduces the secretion of TNF-a from monocytes/macroph-ages (131) and is also able to reverse some ofthe deleterious effects induced by this cytokine on the endothelium. For instance, adiponectin inhibits the TNF-a-induced expression of ICAM-1, VCAM-1, and E-selectin (132) and prevents the attachment of monocytes to the endothelial surface (Fig. 4). Inhibition of nuclear factor-KB signaling by physiological concentrations of adiponectin through a cyclic adenosine monophosphate-depen-dent pathway is considered the underlying molecular mechanism responsible for this action (133). Through the inhibition of class A macrophage scavenger receptor (SR-A) gene expression, adiponectin reduces cholesterol ester accumulation and decreases oxLDL uptake, thereby diminishing the transformation of macrophages into foam cells (134). SMC proliferation and migration induced by heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), EGF, basic fibroblastic growth factor, and platelet-derived growth factor is also suppressed by adiponectin (135). Data on adiponectin-deficient mice have shown a twofold increase in neointimal thickening and increased proliferation of

Fig. 4. Protective action of adiponectin in the initiation and progression of atherosclerosis through anti-inflammatory and antiatherogenic effects. NO, nitric oxide. (Reprinted from ref. 128 with permission from Elsevier, Copyright 2005.)

VSMCs in arteries after mechanical injury (135,136). In addition, adiponectin knockout mice have shown high levels of TNF-a mRNA in adipose tissue (137).

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Supplements For Diabetics

Supplements For Diabetics

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