Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a tissue-specific and inducible transcriptional coactivator for several nuclear receptors and plays a key role in energy metabolism, hepatic gluconeogenesis, and cholesterol homoeostasis. ZLN005 is a small molecule that stimulates the expression of PGC-1α and downstream genes in skeletal muscle cells, improving glucose utilization and fatty acid oxidation at a concentration of 20 μM. Chronic administration of 15 mg/kg/day ZLN005 to diabetic db/db mice increased PGC-1α and downstream gene transcription in skeletal muscle, increasing fat oxidation and improving glucose tolerance, pyruvate tolerance, and insulin sensitivity.
