Adipose tissue is not simply an inert storage depot for lipids but is also an important endocrine organ producing hormones that plays a key role in the integration of endocrine, metabolic, and inflammatory signals for the control of energy homeostasis and the overall inflammatory state. These bioactive proteins have been collectively named adipocytokines. Since the discovery of adiponectin more than 20 years ago, an wealth of knowledge has been gained in elucidating the underlying biology of adiponectin's broad effects. Adiponectin is unique among the adipocytokines in its multiple beneficial actions in protecting against obesity-related complications.
In addition to its well-characterized and broad anti-inflammatory effects on multiple organs, adiponectin modulates the response to tissue injury to promote cell regeneration, inhibit generation of reactive oxygen species, and suppress the fibrotic response. This anti-fibrotic action is mediated directly via inhibition of profibrotic mediators such as transforming growth factor-b (TGF-b) and focal adhesion kinase (FAK), and inhibition of fibroblast activation, as well as indirectly, by inhibiting excessive local inflammation and reducing cell damage.
However, the development of adiponectin protein as a drug complicated by the presence of multiple adiponectin oligomeric isoforms, by its relative insolubility, and by cell-type-specific effects in different tissues.
ALY688 is a bioengineered synthetic peptide designed to be a potent and specific adiponectin mimetic. As such, it works through the same pathways as natural adiponectin to activate intracellular signaling networks to regulate cellular energy utilization, inhibit inflammatory response, and reduce fibrosis.
The wide-ranging biological actions of adiponectin (and ALY688) offers potential therapeutic application across a range of common and rare diseases dominated by excessive and damaging inflammation and fibrosis.