| Objective: In recent years,the incidence rate of type 2 diabetes mellitus(T2DM)is increasing rapidly in China,and it shows a trend of becoming younger.Epidemiological evidence shows that the epidemic trend of T2 DM is consistent with the epidemic trend of obesity,and about 90% patients with T2 DM are obese.T2 DM with obesity is a kind of progressive disease,inadequate insulin secretion and peripheral insulin resistance cause disorders of glucose and lipid metabolism,and lead excessive fatty acids are deposited in non-adipose tissues in the form of TG,it will lead to steatosis of liver cells and the formation of non-alcoholic fatty liver disease.In addition to the traditional diet control and drug therapy,bariatric surgery has become one of the important means to treat T2 DM with obesity.It has been proved that Roux-en-Y gastric bypass(RYGB)can reduce blood glucose,improve lipid metabolism disorder and reduce hepatic fat accumulation,but the mechanism is unclear.The liver plays an important role in fat metabolism,which is closely related to sympathetic nerve activity.This study observed the changes of hepatic lipid metabolism and sympathetic nerve activity 2 weeks after RYGB in T2 DM rats,and changes of hepatic lipid metabolism after the hepatic sympathetic nerves blocked,aiming to explore the possible mechanism that RYGB surgery reduces hepatic fat accumulation and provide a basis for clinical treatment.Materials and methods: Forty male Sprague-Dawley(SD)rats,aged 5 to 6 weeks,weighing 180 to 200 g,were fed in SPF grade animal laboratory.Eight SD rats were randomly selected as a normal control group,and the other rats were fed a 45% high-fat diet.After 4 weeks,intraperitoneal injection of streptozotocin(STZ)(30 mg/kg)was given,then we continued high-fat feeding and monitored blood glucose after 3 days.When rats had random blood glucose ? 16.7 mmol/L and remained stable for 4 weeks,they were considered diabetic and were randomly divided into four groups: diabetic group(n=8),diabetic RYGB sham group(n=8),diabetic RYGB group(n=8)and sympathetic denervation group(n=8).In diabetic RYGB group the proximal portion of the stomach was cut in an arc below the cardia to preserve 20% of the stomach and the distal gastric stump was closed with 6-0 suture.Jejunum was severed about 15 cm from the distal end of Treitz,anastomosis was performed between the distal jejunum and the gastric capsule,and anastomosis was performed between the proximal and distal jejunum at 10 away cm from the anastomotic site.In the RYGB sham group,the stomach and jejunum were severed at the same location as those in the RYGB group and were performed in situ suture.In sympathetic denervation group 90% phenol was applied to the bile duct,portal vein and hepatic artery to block the hepatic nerves after RYGB surgery.After surgery the rats were fed with 45% high-fat diet,and their blood glucose,food intake and body weight were monitored.The fat and muscle content of rats 2 weeks after operation were analyzed by dual-energy X-ray absorbtiometry.TG and FFA levels in liver were examed.The protein expressions of p-HSL,CPT1 A and TH in liver were detected by Western blot.And the concentration of NE in plasma was detected by ELISA.Results:(1)The food intake and the weight of the rats decreased significantly and the blood glucose was close to normal(6.16±1.30).(2)Compared with the diabetic group and the RYGB sham group,in the RYGB group the fat content of rats was significantly reduced(P<0.05),while there was no difference in the muscle content in each group.The hepatic TG content decreased more than 70%(P<0.05),and the hepatic FFA level decreased nearly 50%.(3)The protein expressions of p-HSL and CPT1 A in liver increased more than 1 times(P<0.05),and the protein expression of TH increased significantly increased 2 weeks after surgery(P <0.05).(4)When the hepatic sympathetic nerves were blocked after surgery,the protein expressions and the p-HSL and TH significantly decreased,and the TG content in the liver tissues increased significantly(P <0.05).Conclusion: RYGB surgery can reduce the lipid accumulation in liver and improve the disorder of liver fat metabolism.RYGB surgery can up-regulate hepatic sympathetic nerve activity in a short time,and enhance the activity of p-HSL in liver. |
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