13 Jurnal Anatomi Indonesia, Vol. 2 No. 01 Agustus 2007 Jurnal Anatomi Indonesia VOLUME 02 No. 01 Agustus 2007 Halaman 13 - 17 Role of Adiponectin in Atherosclerosis Evy Sulistyoningrum*, Rina Susilowati** * Pascasarjana Ilmu kedokteran dasar dan biomedis, Universitas Gadjah Mada Yogyakarta ** Bagian Histologi dan Biologi Sel, Universitas Gadjah Mada, Yogyakarta Introduction Adipose tissue has traditionally been considered as an energy storage organ but recently, it is also considered as a hormonally active system in the control of metabolism. Adipose tissue secretes a large number of factors with diverse functions. These factors include free fatty acids (FFA) and protein, which act in autocrine, paracrine, or endocrine manners to control various metabolic functions. 1,2 The terms ‘adipocytokines’ have been used to refer to a number of adipocyte-derived biologically active molecules which may influence the function as well as the structural integrity of other tissues. Some examples of these substances are leptin, TNF-, resistin and interleukin-6. 1,2,3 Leptin is an adipocyte-derived peptide hormone with central and peripheral effects on energy balance. 2 Another product of adipose tissue is Tumor Necrosis Factor- (TNF- ), which is a pro-inflammatory cytokine that has been implicated in the pathogenesis of insulin resistance through increasing release of FFA by adipocytes, reduction in adiponectin synthesis and impairment of insulin signaling. On the other hand, IL-6 is a pleiotropic circulating cytokine with effect from inflammation to host defense to tissue injury. IL-6 also has glucoregulatory effect and increases circulating FFA. 1,3 Adiponectin is a recently discovered adipocy- tokine, and its plasma level is negatively-correlated with body mass index. Furthermore, the plasma level of adiponectin is also decreased in many obesity- related diseases like diabetes, insulin resistance and coronary artery diseases. The physiological role for adiponectin and its role in many pathological conditions have not fully established. Adiponectin increases tissue oxidation which leads to decreasing FFA level and tissue trigliserides, and furthermore increases insulin sensitivity. Data from animal studies, adiponectin has anti-diabetic activity 4 and anti-atherogenic property in certain species. 4,5,6 In populational studies, plasma level of adiponectin can predict incidence of metabolic syndrome in youth, 7 also, higher level of adiponectin were associated with lower risk for coronary heart disease. 8 This brief article will review the current understanding about the structure, function, and effects of adiponectin on atherosclerosis and provide insight into its potential therapeutic and prognostic relevances. The Discovery and Molecular Structure of Adiponectin Adiponectin is known by multiple names which are Acrp30, AdipoQ, apM1 and gelatin-binding protein 28 (GBP 28). This adipose tissue-specific protein is abundant in plasma, accounting for up to 0.05% of total serum protein. 1 Scherer et al. (1995) 9 described a novel 30-kDa secretory protein that is made exclusively in adipose tissues, which is structurally similar to complement factor C1q. Therefore, adiponectin is called Acrp30 (adipocyte complement- related protein of 30 kDa). Northern blot analyses showed that Acrp30 contained H” 244 amino acids, which can be distinguished in four domains: amino- terminal signal sequence, a variable region, a collagenous domain and a carboxy-terminal globular domain homologous with globular domain of the subunits of complement factor C1q. Plasma concentration of adiponectin is 5-30 μg/ ml. 1,2 Adiponectin can be found in several forms. Adiponectin monomer can exist as the full length or globular fragment, but most of adiponectin exist as full length structure, only a small amount of globular adiponectin in the plasma. 10,11 Monomeric-full length adiponectin has not been observed in the circulation and appears to be confined to the adipocyte. 10 Monomeric structure of adiponectin and its domains are shown in Figure 1.