Adiponectin, a secretory protein specifically expressed by adipose tissue, has been shown to play a critical role in the maintenance
of metabolic homeostasis. A deficiency of adiponectin has been linked to a wide variety of metabolic abnormalities, including obesity
and associated disorders such as insulin resistance, hyperglycemia, dyslipidemia, hypertension and nonalcoholic fatty liver disease,
collectively referred to as the “metabolic syndrome”. Conversely, increased expression of adiponectin corrects these abnormalities, as revealed
by the positive metabolic effects observed in genetic over expression studies or by administration of recombinant adiponectin.
This has led to widespread interest in its role as a therapeutic target for treatment of a range of metabolic disorders such as diabetes mellitus,
obesity, inflammatory and cardiovascular diseases. Various therapeutic approaches targeted at increasing adiponectin levels, or its activity,
are being explored. These consist of increasing expression of adiponectin or its receptors by inducers, increasing circulating levels
of adiponectin by administering recombinant protein, peptide mimetic approaches, or increasing expression/activity of its downstream effectors
such as AMPK or PPAR alpha. Many of these approaches have achieved therapeutic benefits in animal models of metabolic diseases.
Despite the profusion of research on adiponectin and ways to modulate it, there are limited number of studies focused on smallmolecule
based-therapeutic approaches. In this review, we summarize what is currently known with respect to the therapeutic potential of
adiponectin and discuss the challenges in designing small molecule-based therapies.