| Objective To investigate the effect of Baoyuan Jiedu Decoction on serum lipids and white adipose tissue browning in cancer cachexia mice.Methods The mice were divided into normal group,model group,BJD group and MA group.Except the normal group,the animal model of cancer cachexia was induced by Lewis lung cancer cells.After 21 days of intervention,the changes of body weight,food intake,water consumption;tumor volume and general conditions of the mice were observed;the contents of IL-6 and PTHrP in serum were detected by ELISA;multidimensional mass spectrometrybased shotgun lipidomics(MDMS-SL)was used to determine the changes of 9 kinds of lipids in the serum of mice,including Car,Cer,FA,PC,PI,PE,SM,LPC,LPE;white adipose tissue morphology and lipid droplet area were detected by HE staining;the expressions of white adipose tissue browning related genes were detected by RT-PCR;and the protein expression of UCP1 of cancer cachexia mice were detected by Western Blot and IHC staining.Results 1.1.Compared with the model group,the mice in BJD group were generally in good condition,and their weight increased significantly(P<0.05),and their food intake and water intake were increased significantly(P<0.05),and the volume of tumors were significantly suppressed(P<0.05);BJD also significantly reduced the content of IL-6 and PTHrP(P<0.05)in serum of mice compared with the model group.A total of 237 lipids of 9 classes were detected from mouse serum by MDMS-SL,including 8 ceramides,19 phosphatidylinositols,49 phosphatidylcholines,55 Phosphatidylethanolamines,15 lysophosphatidylcholines,23 lysophosphatidyl ethanolamines,26 sphingomyelins,22 carnitines and 20 fatty acids,among which carnitines and fatty acids are the most abundant.PCA analysis was used to analyze the quality control of the data.The results showed that there were significant differences in the serum lipids among three groups.After BJD treatment,the serum lipids of mice changed and tended to be consistent with the trend of the normal group,indicating that BJD could improve the abnormal changes of the serum lipids of the cancer cachexia mice.One Way ANOVA was used to filter the significantly different lipids in the groups in the serum of mice based on P<0.05.Compared with the normal group,there were 61 kinds of lipids were increased or decreased in the model group,including 6 sphingomyelins,8 lysophosphatidylcholines,18 Phosphatidylethanolamines,2 ceramides 3 phosphatidylinositols,5 lysophosphatidylcholines,4 carnitines and 15 fatty acids.And the intervention of BJD affected 30 kinds of abnormal lipids among the disorder including 3 lysophosphatidylcholines,9 phosphatidylethanolamine,1 ceramides,4 lysophosphatidylcholines,3 carnitines and 10 fatty acids.2.Compared with the model group,BJD alleviated the mass loss of white adipose tissue(P<0.05)and the results of HE staining showed BJD improve lipid droplets(P<0.05)in iWAT and eWAT.Compared with the model group,BJD could inhibit the expression of browning related genes UCP1,Cidea and Prdm16(P<0.05)and the expression of browning marker protein UCP1(P<0.05)in eWAT and iWAT of cancer cachexia mice.Conclusion 1.BJD can improve the diet,water drinking and general survival of cancer cachexia mice.Also,it can inhibit weight loss and tumor volume of cancer cachexia mice and significantly inhibit the content of IL-6 and PTHrP in serum of cancer cachexia mice.2.In this study,MDMS-SL technology was used and found out significantly different lipids changes in the serum of cancer cachexia mice.BJD can effectively improve the abnormal changes of serum lipids in cancer cachexia mice.3.BJD could effectively improve the weight loss and fat drop area of eWAT and iWAT.Furthermore,BJD could inhibit the expression of UCP1,Cidea and Prmd16 mRNA,and protein UCP1 expression,preventing white adipose tissue browning in eWAT and iWAT of cancer cachexia mice. |
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