Gandou Decoction Regulates Liver Lipid Metabolism in a Mouse Model of Wilson's Disease via the Peroxisome Proliferator-activated Receptor Gamma-Cluster of Differentiation 36 Pathway
Objective To investigate the regulatory effect of Gandou Decoction on liver lipid metabolism in Wilson's disease (WD)mice and its mechanism.Methods A total of 10 DL mice were used as normal group,and 20 TX mice were randomly di-vided into model group and Gandou Decoction group,with 10 mice in each group.The mice in the model group and the normal group were given normal saline 25 mL/(kg·d)by gavage for 4 weeks,and those in the Gandou Decoction group were given Gandou Decoction 18.5 g/(kg·d)by gavage for 4 weeks.Inductively coupled plasma mass spectrometry was used to measure the content of copper in the liver;a biochemical analyzer was used to measure the serum levels of serum total cholesterol (TC),triglycerides (TG),low-density lipoprotein cholesterol (LDL-C),alanine aminotransferase,and aspartate aminotransferase;the content of malondialdehyde (MDA)in liver tissue was measured to evaluate the degree of lipid peroxidation in the liver;oil red O staining was used to observe liver lipid deposition;RT-qPCR was used to measure the mRNA expression levels of lipid me-tabolism-related proteins[adipocyte TG hydrolase (ATGL),fatty acid synthase(FASN),acetyl-CoA carboxylase 1 (ACC1 ),and sterol regulatory element-binding protein-1 c(SREBP-1 c)],peroxisome proliferator-activated receptor gamma (PPAR γ),and cluster of differentiation 36 (CD36 )in liver tissue,and Western blot was used to measure the protein expression levels of PPARγ and CD36 in the liver.Results Compared with the normal group,the model group had a significant increase in the con-tent of copper in the liver(P<0.05),and compared with the model group,the Gandou Decoction group had a significant reduc-tion in the content of copper in the liver(P<0.05).Compared with the normal group,the model group had significant reduc-tions in the serum levels of TG,TC,and LDL-C(P<0.05),and compared with the model group,the Gandou Decoction group had significant increases in the serum levels of TG,TC,and LDL-C(P<0.05).The model group had a significant increase in the content of MDA in the liver compared with the normal group (P<0.05),and the Gandou Decoction group had a significant re-duction in the content of MDA compared with the model group(P<0.05).Oil red O staining showed that the model group had extensive lipid deposition,and compared with the model group,the Gandou Decoction group had a significant reduction in the ar-ea of lipid droplets in the liver(P<0.05).Compared with the normal group,the model group had significant increases in the mRNA and protein expression levels of PPARγ and CD36 in the liver(P<0.05)and significant reductions in the expression levels of ATGL,FASN,ACC1,and SREBP-1c(P<0.05);the Gandou Decoction group had significant reductions in the mRNA and protein expression levels of PPARγ and CD36 in the liver(P<0.05),significant increases in the mRNA expression levels of ACC1,FASN and SREBP-1c(P<0.05),and a significant reduction in the mRNA expression level of ATGL(P<0.05).Conclusion Gandou Decoction can improve abnormal liver lipid metabolism and reverse the progression of hepatic steatosis in a mouse model of Wilson's disease by regulating the PPARγ-CD36 pathway.
Wilson's diseaseLipid metabolismGandou DecoctionPeroxisome proliferator-activated receptor gammaCluster of differentiation 36
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