Irisin as a performed monomer for adipocyte browning

4^th International Conference on Medicinal Chemistry & Computer Aided Drug Designing

November 02-04, 2015 Atlanta, USA

Lu Zhai1, Ling Wu1, Catie Sheldon2, Feng Li1, Anne Brown1, David Bevan1, Andrew Herr2 and Bin Xu1

1Virginia Tech, USA 2Cincinnati Children��?s Hospital Medical Center, USA

Posters-Accepted Abstracts: Med chem

Abstract :

Exercise has well-recognized beneficial effects on system metabolism. Irisin was recently identified as an exercise-induced peptide hormone secreted by skeletal muscle in mice and humans. The hormone is thought to bind to so far unidentified surface receptor on white fat cells and induces â�?�?browningâ�? effects that improve the tissue metabolic profile and increase whole-body energy expenditure. As a potential new anti-obesity and anti-diabetes target, this peptide hormone is however poorly characterized. We have successfully manufactured recombinant irisin, which provides a key reagent for detailed biochemical, biophysical, and pharmacological characterizations. Wild type irisin exists in the form of dimer in solution. Through structure-based computational modeling and systematic surface mutagenesis, we have mapped out the detailed dimeric interface and engineered monomeric irisin variants. The interface is consistent with what was identified by X-ray crystallography. Several monomeric irisin variants have been engineered and identified. Circular dichroism analyses suggest marked differences comparing monomer variants to dimer variants. A sensitive adipocyte-based functional assay has been established in our laboratory. Based on the cell-based functional assay and signaling activation assay, we identified several active monomeric variants including a highly active monomer variant. A model of how irisin molecule activates adipocyte browning program has been proposed.

Biography :

Email: luzhai@vt.edu