PEG-BHD1028 Peptide Regulates Insulin Resistance and Fatty Acid β-Oxidation, and Mitochondrial Biogenesis by Binding to Two Heterogeneous Binding Sites of Adiponectin Receptors, AdipoR1 and AdipoR2

Adiponectin plays multiple critical roles in modulating various physiological processes by binding to its receptors. The functions of PEG-BHD1028, a potent novel peptide agonist AdipoRs, was evaluated using vitro and vivo models based on the reported action spectrum adiponectin. To confirm design concept sites their affinities were analyzed SPR (Surface Plasmon Resonance) assay. results revealed that PEG-BHD1028 bound two heterogeneous AdipoR1 AdipoR2 with relatively high affinity. In C2C12 cells, significantly activated AMPK subsequent pathways enhanced fatty acid β-oxidation mitochondrial biogenesis. Furthermore, it also facilitated glucose uptake lowering insulin resistance insulin-resistant cells. reduced fasting plasma level db/db mice following single s.c. injection 50, 100, 200 μg/Kg tolerance at dose 50 decreased production. animals received 5, 25, for 21 days lost weight after 18 range 5–7%. These imply development as potential adiponectin replacement therapeutic agent.