db/db mice: 15 mg/kg/day was administered orally for 6 weeks

The transcriptional modulatory effect of ZLN005 in L6 myotubes was investigated. ZLN005 increased peroxisome proliferator–activated receptor-γ coactivator-1α (PGC-1α) mRNA levels in a dose-dependent manner; 20 μmol/L ZLN005 caused a threefold increase over the control after 24 h. At 10 μmol/L, the PGC-1α mRNA levels were increased to almost the same extent at 16 to 48 h. ZLN005 stimulated glucose uptake dose dependently after 24 h of treatment, with 20 μmol/L of ZLN005 resulting in a 1.8-fold improvement. Because the induction of the expression of genes involved in mitochondrial biogenesis and fatty acid oxidation (FAO) was observed. ZLN005 increased oxidation of palmitic acid dose dependently, with 20 μmol/L ZLN005 resulting in a 1.28-fold increase after 24 h compared with control. These results demonstrated that ZLN005 stimulated the expression of PGC-1α and downstream genes in skeletal muscle cells and improved glucose utilization and FAO.