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Effect of Grape Seed Proanthocyanidin Extract on Renal Lipid Deposition in db/db Mice
Du Chunyang, Yao Fang, Ren Yunzhuo, Wu Haijiang, Wu Ming, Han Weixia, Duan Huijun, Shi Yonghong*
Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China
Abstract: The purpose of this study is to investigate the role of the grape seed proanthocyanidin extract (GSPE) on renal lipid deposition in db/db mice. Sixteen male db/db mice were randomly divided into two groups: diabetic nephropathy group (db/db， n=8) and grape seed proanthocyanidin extract treatment group (db/db+GSPE， n=8). Sixteen male non-diabetic littermate db/m mice were also randomly divided into two groups:control group (db/m， n=8) and grape seed proanthocyanidin extract treatment control group (db/m+GSPE， n=8).Eight weeks after treatment， fasting blood-glucose (FBG)， blood urea nitrogen (BUN)， serum creatinine (Scr)，total triglycerides (TG)， total cholesterol (TC) and urinary albumin excretion (UAE) were detected by semiautomatic biochemical analyzer. Expression of sterol regulatory element binding protein-1 (SREBP-1)， fatty acid synthase (FASN)， acetyl-CoA carboxylase (ACC)， peroxisome proliferator-activated receptor α (PPARα)，carnitine palmitoyltransferase 1 (CPT1) and acyl-coenzyme aoxidase 1 (ACOX1) in kidney tissues were detected by Western blot and Real-time PCR. Lipid droplets formation in renal tissues were observed by Oil Red O staining and transmission electron microscopy. Compared with db/m mice， the levels of FBG， BUN， Scr， TG， TC and UAE were significantly increased in db/db group， while db/db mice treatment with GSPE exhibited a remarkable decrease on these parameters. The results of the ransmission electron microscopy and Oil Red O staining revealed that GSPE prevents lipid droplets formation in the tubular cells of diabetic db/db mice. In addition， up-regulation of SREBP-1， FASN and ACC and down-regulation of PPARα， CPT1 and ACOX1 induced by diabetes were markedly prevented by treatment with GSPE (P<0.05， P<0.01). These findings indicated that GSPE inhibited renal lipid deposition in db/db mice through inhibition of fatty acid synthesis and promotion of fatty acid β oxidation.
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