A novel triazine ring compound (MD568) exerts in vivo and in vitro effects on lipid metabolism

In this study, we investigated the toxicity and biological activity of a novel triazine ring compound named magnolol derivative 568 (MD568). The LD₅₀ of MD568 was determined in Sprague-Dawley (SD) rats by intraperitoneal injection. Treatment of high fat diet-induced obese rats with MD568 demonstrated that MD568 displayed significant anti-obesity effects. MD568 markedly reduced body weight, blood lipid contents, white adipose tissue (WAT) and liver mass in obese rats. In addition, MD568 modulated lesions in WAT through regulating PPAR-Ɣ, C/EBP-a, SREBP-1c and FABP-4 proteins in the liver through regulating PPAR-α, SREBP-1c and FABP-4. We also evaluated the effects of MD568 on the proliferation and differentiation of 3T3-L1 pre-adipocytes and investigated the underlying mechanism by microarray analysis. Results showed that MD568 has good inhibitory activity on lipogenesis and lipid accumulation in 3T3-L1 pre-adipocytes. The protein expression levels of the adipogenic transcription factors PPAR-Ɣ, C/EBP-a, SREBP-1c and FABP-4 were reduced by MD568. In addition, the gene expression of FAS and LDL was also significantly down-regulated by MD568. Microarray data enrichment analysis demonstrated that the underlying mechanism of action of MD568 may be related to its regulatory effects on genes associated with the biological processes or pathways in lipid metabolism.