Vertical Sleeve Gastrectomy Reverses Hepatic Steatosis By Targeting CASP8 And FADD-like Apoptosis Regulator

Part ⅠVertical Sleeve Gastrectomy improved the hepatic steatosis in obese subjectsObjective: To study the changes of hepatic steatosis in patients with obesity undergoing VSG.Material and methods:The abdominal CT images before and after gastric cuff surgery were compared in obese patients to analyze the changes of hepatic steatosis.Obtaining obese patients who met the criteria as a research object,and collecting preoperative and postoperative abdominal CT images,body weight,fasting blood glucose,total cholesterol,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,triglycerides and total bile Acid-related examination results,mainly using computed tomography tools to analyze the changes of hepatic steatosis,as well as the abdominal wall depth,visceral adipose tissue and subcutaneous adipose tissue.Further analysis and research on the changes of postoperative patient related parameters were conducted.Results: CT image analysis showed that the hepatic steatosis status of obese patients after VSG was greatly improved.The liver/spleen ratio of obese patients was significantly higher than that of preoperative(0.824 vs 0.437,p<0.05).In addition,preoperative body mass index(38.7 vs 35.3 kg/m2,p<0.01),abdominal wall thickness(4.54 vs 4.06 cm,p<0.01),visceral adipose tissue(179.73 vs 104.69 cm2,p<0.05)and subcutaneous adipose tissue(423.08 vs 345.92 cm2,p<0.05)were significantly reduced after surgery.Conclusions: VSG significantly improved hepatic steatosis status in obese patients,reducing body mass index and visceral and subcutaneous fat tissue.Part Ⅱ VSG reverses hepatic steatosis in obese mice by regulating CFLAR expression in liverObjective: To study the effects of VSG on fatty liver in obese mice and the regulation of hepatic fat metabolism,fasting blood glucose regulation and CFLAR expression.Material and methods : After establishing the hepatic steatosis model of obese mice,the obese mice were randomly divided into the operation group,the sham operation group,and the untreated group.Another normal diet group was set up,followed by VSG.After eight weeks post surgery,the changes of hepatic steatosis in the operation group and the sham operation group were compared by HE and Oil Red O.The changes of body weight in different groups were compared.The blood glucose level of the operation group and the sham operation group was compared by blood glucose meter.Oral glucose tolerance test was carried out and the insulin in plasma was detected by ELISA and the insulin resistance index was calculated.The content of triglyceride and non-esterified fatty acid in liver were detected by lipid metabolism test kit.Total cholesterol and triglycerides in plasma were detected by ELISA kit.The m RNA changes of fat metabolism enzymes FAS and CFLAR were analyzed by RT-PCR.The changes of FAS,CFLAR and glucose metabolism related proteins(p-JNK,p-STAT3)were analyzed by Western blotting.Results: The liver HE staining of the obese mice underwent VSG showed that the fat vacuole was significantly lower than that of the sham operation group.The ORO staining showed that the fat staining area was significantly lower than that of the sham operation group.The weight of the mice in the surgery group was significantly lower than that in the sham operation group at 8weeks after surgery.The visceral adipose tissue(1.37 vs 5.33g)and subcutaneous adipose tissue(1.20 vs 6.63g)in the operation group were significantly lower than the sham operation group.The fasting blood glucose in the operation group was significantly lower than that in the sham operation group two weeks after surgery.Compared with the sham operation group,the OGTT and HOMA-IR of the operation group were significantly lower than that of the sham operation group.The levels of NEFA and TG in the liver of VSG mice group were significantly lower than those in the sham operation group,and the total cholesterol and triglyceride in the plasma were also significantly lower than those in the sham operation group.RT-PCR results showed that the expression of CFLAR m RNA in the liver of VSG mice was significantly higher than that in the sham operation group.The results of Western Blot showed that the expression of CFLAR protein in the liver of the operation group was significantly enhanced compared with the sham operation group and the untreated group.At the same time,RT-PCR results showed that the fasn of the VSG group was lower than that of the sham operation group.The results of Western Blot showed that the FAS of the operation group was lower than that of the sham operation group.The phosphorylated protein p-JNK associated with glucose metabolism was significantly reduced in the VSG group compared with the sham operation group,and the downstream phosphorylated protein p-STAT3 was correspondingly increased in the surgical group.Conclusions: Hepatic steatosis was reversed in VSG group compared with sham operation group,blood glucose metabolism was significantly improved.Liver and plasma lipid levels were significantly improved,liver CFLAR expression was significantly enhanced,and liver fat metabolism enzyme FAS was significantly reduced.Part Ⅲ CFLAR inhibits the accumulation of lipids in liver cellsObjective: To study the effects of CFLAR on lipid metabolism in liver cells and the mechanism.Material and methods:Exogenous palmitate(PA)was used to mimic high lipid metabolism environment,and high-expression CFLAR plasmid was used to establish liver cells with high expression of CFLAR.Western blot was used to test the expression of CFLAR in the environment with lipid to confirm the inhibition of CFLAR expression by high lipid metabolism.The expression levels of FAS and p-JNK in the high expression CFLAR and blank hepatocytes with palmitate were detected by Western Blot.Oil Red O staining was used to determine the lipid accumulation in highly expressed CFLAR hepatocytes with palmitateResults: The expression of CFLAR in hepatocytes was inhibited in the high lipid metabolism environment simulated by palmitate,and the lipid accumulation effect of hepatocytes transfected with high expression of CFLAR plasmid in palmitate environment was significantly weaker than that in the blank group.Hepatocytes with high expression of CFLAR have a lower lipid metabolism enzyme FAS in the palmitate environment than the control group,and the phosphorylated protein p-JNK associated with glucose metabolism is also reduced.Conclusions: High expression of CFLAR hepatocytes inhibits lipid metabolism and reduces lipid accumulation.