As discussed above, promising results obtained from numerous animal experiments and human epidemiological studies support the role of adiponectin as a potential drug target for developing novel therapeutics against a panel of obesity-related chronic diseases. However, adiponectin is an abundant plasma protein (5-30 p.g/mL). The production of recombinant adiponectin is also challenging because of the complex tertiary and quaternary structure of the protein and the distinct activities of the different isoforms. Direct supplementation of recombinant adiponectin in human subjects would be extremely expensive. An alternative approach is to use pharmacological or dietary intervention to increase the suppressed endogenous adiponectin production in obesity, or to enhance adiponectin actions in its target tissues. In this respect, it is interesting to note that the PPARy agonists thiazolidinediones (TZDs), such as rosiglitazone and pioglita-zone, which increase adiponectin production in both humans and rodents, demonstrate many of the therapeutic effects of adiponectin, such as insulin-sensitizing, vasoprotec-tive, and anti-inflammatory properties (13,17). Whether the therapeutic effects of the PPARy agonists are mediated via induction of adiponectin remain to be investigated. In addition, metformin, another commonly used antidiabetic drug, has been shown to mimic the action of adiponectin in stimulating AMPK in liver (104).
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