Adiponectin is an antidiabetic adipokine secreted from adipocytes. AdipoR1 and AdipoR2 are the major adiponectin receptors (AdipoR) that activate the AMPK pathway and the PPAR-α pathway, respectively. AdipoRon is a small-molecule AdipoR agonist that binds to AdipoR1 and AdipoR2 with dissociation constant (Kd) values of 1.8 and 3.1μM, respectively, and Rmax values of 14.6 and 8.6 resonance units, respectively. Treatment of C2C12 myotubes with 5-50μM AdipoRon led to an increase in AMPK phosphorylation in a dose-dependent manner. AdipoRon also dose-dependently increased PGC-1α expression and mitochondrial DNA content in C2C12 myotubes. Intravenous administration of AdipoRon at a dosage of 50mg/kg body weight significantly induced AMPK phosphorylation in the liver and skeletal muscles of wild-type mice but not Adipor1-/-Adipor2-/- double-knockout mice. In wild-type mice on a high-fat diet, oral administration of AdipoRon (50mg/kg body weight) for 10 days significantly reduced fasting plasma glucose and insulin levels as well as plasma concentrations of triglycerides and free fatty acid. AdipoRon treatment also increased the expression of genes related to mitochondrial biogenesis and fatty-acid oxidation in wild-type mice fed a high-fat diet. Oral administration of AdipoRon for 2 weeks significantly ameliorated insulin resistance, glucose intolerance, and dyslipidaemia in db/db mice fed a normal chow diet.[3]
作用机制
AdipoRon is a small-molecule AdipoR agonist that binds to both AdipoR1 and AdipoR2.[3]
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