**11. Higher order structures**

Initially, three adiponectin molecules associate through disulphide bonds within the collage‐ nous domains of each monomer to form bouquet-like higher order structure, a homotrimer. The trimers continue to self-associate and form hexamers [33].

The levels of the higher order structures are sexually dimorphic [34], where females have increased proportions of the high-molecular weight forms. The varying forms have altered biological activity and therefore may also have separate functions. The gC1q domain and the trimeric forms of adiponectin activate AMP Kinase in skeletal muscle and lead to increased fatty acid oxidation and reduction in glucose concentrations, whereas the hexameric and full length HMW forms are thought to activate nuclear factor kappa B (NF-κB) pathways [35]. The proportion of HMW adiponectin within adipose tissue is higher than in blood plasma, suggesting regulation at the level of secretion and is a mechanism of adiponectin complex distribution. All isoforms of the molecule are stable in circulation having a relatively longer half life (half-life of ~15hrs) [24].
