Hypoglycemic mechanism of modified Gegen Qinlian decoction based on regulating the expression and DNA methylation of cholesterol transporters in the adipose tissue of type 2 diabetes mellitus rats.

OBJECTIVE

To investigate the hypoglycemic mechanism of modified Gegen Qinlian decoction (，MGQD) by examining its regulation of cholesterol transporter expression and DNA methylation, specifically the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type 1 (SR-B1), in epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT) of rats with type 2 diabetes mellitus (T2DM).

METHODS

The control group (CON) consisted of ten Sprague-Dawley (SD) rats fed a standard chow diet, while 80 SD rats were fed a high-fat diet and administered streptozotocin intraperitoneally to induce diabetes. The diabetic rats were randomly assigned to four groups: T2DM, metformin (MET, 200 mg/kg), low-dose MGQD (MGQDL, 5 g/kg), and high-dose MGQD (MGQDH, 10 g/kg), and received treatment via gavage for 14 weeks. Western blot (WB), quantitative real-time polymerase chain reaction (qPCR), and bisulfite sequencing PCR (BSP) were used to analyze protein levels, mRNA expression, and DNA methylation of Ldlr (gene encoding LDLR) and Srb1(gene encoding SR-B1).

RESULTS

MGQD and metformin treatment significantly reduced blood glucose levels, restored LDLR and SR-B1 protein levels in eWAT, and effectively regulated the mRNA expression and non-cytosine-p-guanine (non-CpG) methylation of Srb1 in eWAT. A significant negative correlation was observed between the methylation of Srb1 in eWAT and its mRNA expression. However, MGQD and metformin had no significant effect on the protein levels, mRNA expression, or DNA methylation of Ldlr and Srb1 in iWAT.

CONCLUSIONS

MGQD did not significantly affect LDLR and SR-B1 expression or gene methylation in iWAT. However, its hypoglycemic effect may be linked to cholesterol regulation in eWAT. Potential mechanisms include increased LDLR protein levels, which may enhance cholesterol uptake, and increased Srb1 methylation, which may suppress its expression and consequently reduce cholesterol efflux.