Mechanism Of The Methylprednisolone-induced The Deposition Of Visceral Fat In Rats

Objectives: To investigate the expression of Wnt/β-catenin signaling molecules andlipolytic enzyme ATGL，HSL in the different adipose tissues of Sprague-Dawley(SD)rats after treatment with methylprednisolone. To explore the potential mechanism of themethylprednisolone-induced the deposition of visceral fat in rats.Methods: Thirty one4-month-old female Sprague-Dawley rats were randomly dividedinto two groups, control group (n=15) and methylprednisolone group (n=16). Themethylprednisolone group was intramuscularly injected with15mg/kg ofmethylprednisolone sodium succinate (MPL) twice a week. The control group wasintramuscularly injected isodose physiological saline. The body weight (BW) and foodconsumption were measured once and twice a week respectively. After12weeks, therats were intraperitoneally injected with10%Chloral hydrate before killed. Bloodsamples were collected via cardiac puncture for measurement of blood lipid and fastingblood glucose. The subcutaneous adipose tissue of inguinal region and perirenal fatpads were carefully dissected bilaterally and quickly weighted. A part of subcutaneousadipose tissue (SAT) and perirenal adipose tissue (PAT) were fixed in10%formalinand then stained with H&E, the other adipose tissues were frozen in liquid nitrogen andstored at﹣80℃. Reverse transcriptase polymerase chain reaction (RT-PCR) andWestern Blotting were used to detect the mRNA and protein expression ofWnt/β-catenin signaling pathway related genes such as Wnt10b, β-catenin and DKK1.Protein expression of adipose triglyceride lipase (ATGL) and hormone sensitive lipase(HSL) were examined by Western blotting.Results: Compared with the control group, the food intake, weight gain andhigh-density lipoprotein (HDL) were decreased in the MPL group. Morever, thevisceral fat mass, fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG)and low density lipoprotein (LDL) were significantly higher in MPL group (P<0.05).The perirenal adipocytes and subcutaneous adipocytes in rats treated withmethylprednisolone had significantly smaller diameters than the control group (P<0.01). The average number of perirenal adipocytes and subcutaneous adipocytes on one slidefor the rats treated with methylprednisolone were significantly greater than that ofcontrol rats (P<0.01). Compared with the control group, the mRNA and proteinexpression of β-catenin and Wnt10b genes in SAT and PAT were decreasedsignificantly (P<0.05), while DKK1was increased significantly in the MPL group(P<0.01). In addition, compared with the control group, the protein expression levels ofATGL and HSL increased in the SAT (P<0.05), but decreased in the PAT in the MPLgroup (P<0.01).Conclusions:1. The methylprednisolone can promote adipogenesis by inhibiting theWnt/β-catenin signaling pathway in the SAT and VAT.2. The methylprednisolone can enhance the lipolysis of SAT through up-regulating theexpression of ATGL and HSL. Moreover, the methylprednisolone can reduce thelipolysis of VAT through down-regulating the expression of ATGL and HSL.3. Methylprednisolone-induced the deposition of visceral fat might related to theinhibition of the Wnt/β-catenin signaling pathway and the differential expression ofATGL and HSL between SAT and VAT response to methylprednisolone.