A novel metformin derivative showed improvement of lipid metabolism in obese rats with type 2 diabetes

In this study, we investigated the lipid metabolism regulatory activity of a novel metformin derivative (MD568) and its potential mechanism of action in obese rats with type 2 diabetes mellitus (T₂ DM). Previous gene chip analysis of 3T3-L1 cells have shown that MD568 regulates the transcription of genes involved in the peroxisome proliferator-activated receptor (PPAR) signalling pathway, fatty acid metabolism, and glycerolipid metabolism. In this study, obese T₂ DM rats were treated with MD568 (200 mg/kg) for 8 weeks. Results showed that MD568 significantly reduced the body weight gain, plasma glucose, insulin, total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels. MD568 treatment also improved the insulin resistance of obese T₂ DM model rats. In particular, in white adipose tissue, MD568 inhibited the excessive volume increment of adipose cells by down-regulating the protein levels of CCAAT/enhancer-binding protein-α (C/EBP-α) and PPAR-γ, as well as the transcription of their target lipid metabolism-related genes. In the liver, MD568 inhibited hepatic fatty lesions and interfered with hepatic gluconeogenesis by regulating the expression of lipid metabolism-related genes and glycogen-related kinases. In conclusion, our results suggest that the newly synthesized MD568 affects the maintenance of lipid homeostasis in obese type 2 diabetic rats.