To investigate the effects of Gegen Qinlian Decoction(葛根芩连汤,GQD)on cholesterol levels in inguinal adipose tissue(epididymal white adipose tissue,iWAT)and epididymal adipose tissue(epididymal white adipose tissue,eWAT)of type 2 diabetic rats and to explore the possible mechanism from the viewpoint of DNA methylation of genes encoding key enzymes of cholesterol synthesis.
Rats were divided into 5 groups:control group(CON),type 2 diabetes mellitus model group(T2DM),metformin group(MET),GQD low-dose and high-dose groups(GQDL,GQDH)which were given the corresponding medicines via gavage for 14 weeks. Choelsterol levels were determined by spectrophotometer. Western blot(WB),Quantitative Real-time PCR(QPCR)and Bisulfite sequencing PCR(BSP)were used to detect protein,mRNA expression and DNA methylation respectively.
Both MET and GQDH could effectively reverse cholesterol levels of iWAT and eWAT in diabeteic rats. Moreover,GQDL could effectively reverse cholesterol levels of eWAT. GQDL and GQDH effectively elevated the protein expression levels of Hmgcr inWAT and eWAT,however,treatment groups didn’t exhibit the increase of the mRNA expression of genes encoding key enzymes of cholesterol synthesis. CAs methylation of Hmgcr in iWAT and eWAT and CG3 methylation of Hmgcr in eWAT were correlated with FBG,GSP or insulin of serum. Furthermore,CG3 methylation of eWAT in T2DM group was significantly reduced,while CAs methylation of eWAT in MET group was significantly increased.
The effect of GQD or MET on reversing cholesterol level in adipose tissue of diabetic rats may not be achieved by regulating the biosynthesis of the cholesterol. However,GQD may promote the nonsterol branch of mevalonate pathway by post-transcriptional regulation of Hmgcr. The hypomethylation of CAs and CG3 in adipose tissue may be closely related to the progress of diabetes mellitus.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |