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Overview
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Background
ZLN005 is a novel transcriptional regulator of PGC-1α [1].
Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is an inducible coregulator that regulates energy metabolism. PGC-1α regulates glucose and fatty acid metabolism, mitochondrial biogenesis and so on. Dysregulation of PGC-1α is correlated with insulin resistance and type 2 diabetes mellitus [1].
ZLN005 is a novel PGC-1α transcriptional regulator. In the PGC-1α promoter reporter assay, ZLN005 potently inhibited luciferases. In L6 myotubes, ZLN005 dose-dependently increased PGC-1α mRNA levels. ZLN005 (10 μM) increased the mRNA levels of cytochrome c oxidase 5b (cox5b), acyl-CoA oxidase, strogen-related receptor α (ERRα), NRF1 and GLUT4. ZLN005 (20 μM) increased glucose uptake and oxidation of palmitic acid by 1.8-fold and 1.28-fold respectively in a dose dependent way. In L6 myotubes transfected with PGC-1α siRNA, ZLN005-stimulated oxidation of palmitic acid and expression of the PGC-1α gene was blocked. In L6 myotubes, ZLN005 increased the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) [1].
In db/db mice, ZLN005 reduced RER, suggesting a shift to fatty acid use. ZLN005 significantly reduced fasting blood glucose and random blood glucose levels. Also, ZLN005 improved glucose clearance and pyruvate tolerance and reduced insulin resistance [1].
Reference:[1]. Zhang LN, Zhou HY, Fu YY, et al. Novel Small-Molecule PGC-1a Transcriptional Regulator With Beneficial Effects on Diabetic db/db Mice. Diabetes, 2013, 62(4): 1297-1307.
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