| Objective: Obesity is one of the global health threats.Obesity can lead to insulin resistance(IR)and increase the risk of type 2 diabetes mellitus(T2DM).As the number of obese T2 DM patients increases year by year,the prevalence of non-alcoholic fatty liver disease(NAFLD)among obese T2 DM patients exceeds 70%,becoming one of the main associated diseases.Obese patients with T2 MD are often associated with hepatic steatosis due to fat ectopic deposition.NAFLD refers to a clinicopathologic syndrome characterized by diffuse bullous steatosis of hepatocytes,which is caused by alcohol and other definite liver damage factors.These include simple fatty liver disease and its progression to steatohepatitis and cirrhosis.Is more accepted in the pathogenesis of NAFLD is "secondary" theory,for the first time for IR and lipid metabolism disorder,fat cells in the IR help to increase the activity of hormone sensitive lipase,triglyceride(TG)decomposition speed,too much free fatty acid(FFA)are released into the bloodstream after liver cells to absorb,increased liver fat from scratch,lead to hepatocyte fatty degeneration.The second blow is oxidative stress,which refers to the imbalance between the generation and clearance of free atomic groups,and the accumulation of oxidative products leads to tissue damage and the development of liver fibrosis and cirrhosis.It can be seen that IR is the main pathogenesis basis and TG ectopic(liver)accumulation is the primary pathological manifestation.At present,its main treatment methods include lifestyle intervention and drug therapy,but the efficacy is not good.Roux-en-y gastric bypass(RYGB)has been proven to effectively improve IR and fat metabolism disorders in obese T2 DM patients,and can significantly delay or even cure the development of NAFLD.However,the exact mechanism of how RYGB reduces hepatic fat accumulation is still unclear.The liver is the main place to the body to fat metabolism,including hydrolysis pathways,synthesis and secretion pathways in liver fat metabolism disorder of fatty liver plays a significant role in the development of the study will investigate RYGB surgery for T2 DM rat liver fat metabolism pathway and the possible mechanism of the influence of clinical T2 DM and liver fat toxicity and provide reliable theoretical basis for the treatment of IR.Materials and methods: Twenty-four male SD rats(SPF grade)aged from 5 to 6 weeks old and weighing 180 ~ 200 g were selected.SPF animal laboratory,maintaining constantroom temperature and humidity,12-hour round-the-clock cycle,free drinking water.SD rats were given normal feed for adaptive feeding for 1 week,and then each group was replaced with 45% high-fat diet feeding.SD rats in each group were fed a 45% high-fat diet for 4 weeks before they became obese.A reformulated STZ intraperitoneal injection(30mg/Kg)was given.Fasting blood glucose of rats was measured weekly,and plasma concentration of tail vein of rats was measured by rapid glycemic meter.Criteria for successful modeling of obese type 2 diabetes mellitus rats: >16.7mmol/L of blood glucose after intraperitoneal injection of STZ was maintained for more than 4 weeks,indicating successful modeling.Obese T2 DM rats successfully modeled were randomly divided into diabetic group,diabetic RYGB sham group and diabetic RYGB group,with8 rats in each group.RYGB surgical method: the gastric body was cut off with the connection line between the lesser curvature of the stomach and the greater curvature of the stomach as the boundary,and 20% of the small gastric sac was retained.The distal residual stomach was closed with 6-0 suture line.If blood vessels were injured in this process,appropriate electrocoagulation and hematoplexia could be achieved.Jejunal dissection was performed about 10 cm away from the distal end of the Treitz ligament,distal jejunum and small gastric sac were anastomosed,and proximal and distal jejunal anastomosis was performed about 10 cm away from the anastomosis.Rats in the RYGB sham surgery group and those in the RYGB surgery group underwent intestinal dissection at the same site and end-to-end anastomosis in situ.SD rats in each group were fed with 45% high-fat diet for 2 weeks after surgery,and their body weight,blood glucose and food intake were recorded weekly.Body fat and muscle contents in rats were analyzed by dual-energy X-ray technique and body weight before sampling was measured.The contents of TG and FFA in plasma and TG in liver tissue were determined by enzymatic method.Western blot analysis was performed to detect the expression of diglyceryl transferase 2(DGAT2),triglyceride hydrolase(ATGL),phosphorylated hormone-sensitive lipase(p-hsl),microsomal triglyceride transporter(MTTP),microtubule-associated light chain protein(LC3)and selective autophagy adaptor protein(P62)in rat liver.The fat content of liver tissue in each group was observed by oil red O staining.Results :RYGB surgery significantly reduced body weight and adipose tissue content,and significantly improved blood sugar.Compared with the diabetic group and RYGB sham operation group,the TG content in the liver of RYGB group decreased by 87% 2weeks after surgery(P<0.05),indicating that the liver fat content of RYGB group decreased significantly 2 weeks after surgery.DGAT2 protein expression decreased in liver(P < 0.05),P-HSL protein expression increased(P < 0.05),LC3-Ⅱ/LC3-Ⅰ levels(P< 0.05),decrease in P62 protein expression(P < 0.05),indicating that RYGB group of liver fat hydrolysis enzyme and autophagy activity increases significantly,liver fat synthetase dropped significantly.Conclusion: This study investigated the effect of RYGB on hepatic fat metabolism.The above results suggest that RYGB can reduce the toxicity of hepatic lipid and improve the disorder of fat metabolism by up-regulating the autophagy activity of the liver.Postoperative GLP-1 secretion may be one of the mechanisms that activate autophagy. |
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