Effect Of Obesity On Inflammation And Intestinal Barrier And Intervention

Part.1Effect of obesity and intervention of n-3polyunsaturatedfatty acids on intestinal barrierBackground:Growing evidences showed that an important characteristic of obesity is low-grade inflammation. Changes in intestinal barrier, which included the gut microbiota dysbiosis, increased intestinal permeability and elevated endotoxin in blood, thereby triggering the inflammatory response. N-3polyunsaturated fatty acids were used for the treatment and prevention of cardiovascular disease, could reduce the body weight of obese patients, improve the metabolic syndrome. Our previous study showed that there were less contents of n-3PUFAs in the obese patients than non-obese patients. Supplementation of n-3PUFAs can improve the intestinal permeability in the models of inflammatory bowel disease and partial hepatectomy animal, but the effect of n-3PUFAs on the intestinal barrier impaered by high fat died is less reported.Objective:The aim of the present study is to investigate the effect of high fat diet incduced obeisty on the the intestinal barrier and protection effects of supplementation with n-3polyunsaturated fatty acids, which provides theoretical basis for clinical application in the future.Methods:Thirty-six Sprague-Dawley rats were divided into four groups randomly, fed control diet(CD), high-fat diet(HFD), control diet supplemented with n-3polyunsaturated fatty acids and high-fat diet supplemented with n-3polyunsaturated fatty acids respectively. Fresh fecal samples were collected to analyze the gut microbiota after10weeks feeding. DNA was exacted from the fresh fecal samples. Real-time PCR was used to detect the composition of the gut microbiota. The levels of hsCRP, TNF-α and IL-6in plasma were measured through ELISA, respectively. The endotoxin levels were detected though modified azo chromogenic substrate limulus amebocyte lysate assay. Intestinal permeability(lactose/mannitol ratio in the urine, L/M)was determined on the end of this study. Western blotting method was used to detect tight junction protein of intestinal mucosa.Results:The HFD induced a more increase in the body weight than the CD, CD+n-3PUFAs, HFD+n-3PUFAs groups. There were more contents of the Firmicutes, Enterobacteriales, and less contents of Bacteroidetes, Bifidobacterium spp. and ratios of Bacteroidetes to Firmicutes in the fecal of the rats from HFD group compared to the CD and HFD+n-3PUFAs groups. There were more contents of the Bacteroidetes in the fecal of the rats from CD+n-3PUFAs group compared to the CD group. The Pearson’s correlation coefficient shows that there is a negative correlation between the body weight and the ratios of Bacteroidetes-to-Firmicutes. Intestinal permeability(L/M) was increased significantly in HFD group compared to CD and HFD+n-3PUFAs groups, but there is no significant difference in the L/M ratio between the CD and CD+n-3PUFAs groups. The endotoxin and inflammatory factors in plasma in portal vein from rats of HFD group were higher than CD and HFD+n-3PUFAs groups, but expression of claudin and occludin in intestinal mucosa of HFD group were lower than CD and HFD+n-3PUFAs groups.Conclusion:HFD-induced obesity changed the gut microbiota and increased intestinal permeability. Supplement with n-3PUFAs could counteract these gut dysbiosis and reduce the intestinal permeability as well as improve inflammatory factors and the body weight. Part.2Fatty acid composition and estimated desaturase activities in visceral and subcutaneous adipose tissues of morbidly obese patients, and are associated with inflammatory factors and insulin resistanceBackground:Obesity is characterized by abnormal fat storage and low-grade inflammation in adipose tissue and serum. Adipose tissue from obese patients abnormally secretes abundant inflammatory factors that promote the insulin resistance and metabolic syndrome. However, the cause of elevated infalmmatory factors is still unknown. Previous studies showed that fatty acid composition in both blood and adipose tissue reflected the diet intake of fatty acid, and was associated with metabolic syndrome, obesity and inflammatory factors. But the studies on the fatty acid composition in serum and adipose tissue from Chinese morbidly obese patiens are limited.Objective:The objective of this study was to investigate the differences in fatty acid composition and estimates desaturase activities in visceral and subcutaneous adipose tissue between morbidity obese and non-obese subjects, and to investigate the correlation between fatty acid composition and desaturase activities with obesity-associated inflammatory factors, such as high sensitivity C-reactive protein (hsCRP), tumour necrosis factor alpha (TNF-a) and interleukin-6(IL-6) in adipose tissue, and insulin resistance.Methods:Visceral and subcutaneous adipose tissues were obtained from27obese subjects with metabolic syndrome or type2diabetes and24non-obese subjects. Analysis of fatty acid composition in adipose tissue was performed using gas chromatography. The desaturase activities were estimated from the ratio of product to precursor:SCD (C16:ln-7/C16:0and C18:ln-9/C18:0), D6D (C20:3n-6/C18:2n-6) and D5D (C20:4n-6/C20:3n-6). The levels of hsCRP, TNF-a and IL-6in adipose tissue and serum were measured through ELISA, respectively. The differences in fatty acid composition, estimated desaturase activities and inflammatory factors levels between both groups were compared, and the correlations between fatty acid composition and inflammatory factors levels, HOMA-IR were analyzed.ResultscObese subjects had higher levels of oleic (C18:ln-9), palmitic (C16:0), palmitoleic (C16:ln-7) and dihomo--y-linolenic (C18:3n6) acids in both visceral and subcutaneous adipose tissue, and lower levels of stearic acid (C18:0), linoleic acid (C18:2n6) and C18:3n3than the non-obese controls. There were more oleic acid, saturated fatty acids and monounsaturated fatty acids in visceral adipose tissue of obese group, more saturated fatty acids in visceral adipose tissue of non-obese group,compared to subcutaneous adipose tissue. The levels of hsCRP,TNF-a, IL-6and the estimated activities of SCD18and D6D were significantly higher in visceral and subcutaneous adipose tissue of the obese subjects. Also, we found that there were more hsCRP and IL-6in the visceral adipose tissue than in the subcutaneous adipose tissue. hsCRP, TNF-a and IL-6in adipose tissue were positively associated with the cotents of SFAs, MUFAs and estimated activities of SCD18and D6D. hsCRP in adipose tissue was negatively associated with the cotents of n-3PUFAs. HOMA-IR was positively associated with the cotents of SFAs, MUFAs, estimated activities of SCD18and D6D in visceral adipose tissue and estimated activities of D6D in subcutaneous adipose tissue, while it was negatively associated with the cotents of PUFAs and n-3PUFAs in visceral adipose tissue and n-3PUFAs in subcutaneous adipose tissue.Conclusion:There were differences in fatty acid composition and estimated desaturase activities of adipose tissue between obese and non-obese subjects. These difference reflected the a long period of fatty acid intake and metabolism in both groups. Differsence fatty acid composition and inflammtory facors levels between the visceral and subcutaneous adipose tissue showed the discrepant metabolic activities of different fat depots. The high correlations of contents of some fatty aicd and desaturases activities with hsCRP, TNF-a, IL-6in adipose tissue and HOMA-IR suggest that fatty acid intake and metabolsim may play a role in the development of chronic inflammation commonly found in morbid obesity and metabolic syndrome. Part.3Preoperative oral carbohydrate alleviates postoperative insulin resistance and inflammatory reactionBackground:Stress of operation induces postoperative hyperglycemia and inflammatory response that increases the risk of postoperative complications. Long preoperative fasting has been a standard practice for patients undergoing elective surgery to avoid vomiting and pulmonary aspiration during anesthesia induction.In1999, the American Society of Anesthesiologists (ASA) issued a practice guideline for preoperative fasting in which patients (except those with delayed gastric emptying) are allowed to have clear fluids such as water, carbonated beverages until2h before surgery. Preoperative oral carbohydrate administration for adult patients has been recommended by European Society for Parenteral and Enteral Nutrition and Enhanced Recovery After Surgery. Although preoperative oral carbohydrate may improve patient perioperative glucose metabolism, its effects on the gastric contents and anesthesia operation risk remain controversial. Although most domesticphysicians aware of the importance of reduced fasting time and preoperative oral carbohydrate, but management is not implemented considering the operation safety. Therefore, the similar research will contribute to clinical application.Objective:The purpose of the present study is to assess the safety of effect of preoperative oral glucose solution through observe the gastric contents and pH as well as anesthesia and operation complicationson. The effects of preoperative oral blood glucose solution on the perioperative glucose, insulin resistance and inflammatory reaction of ptients after gastrointestinal operation were observed.Methods:48patients received gastrointestinal operation signed informed consent and were randomly divided into the study group (n=23) and the control group (n=25). Patients in study group were given300ml oral administration of25%glucose solution in3hours before operation. Before anesthesia induction, gastric contents were aspirated through nasogastric tube to examine its volume and pH. Serum hsCRP, fasting blood glucose, insulin level and HOMA-IR were detected before operation and in the first morning after operation between both groups.Results:There were no anesthesia and operation complications in both groups. Patients had similar gastric contents volume(30.88±25.93vs27.94±24.04ml) and the pH value of gastric contents(1.99±0.34vs2.13±0.43). There were no significant differences in serum hsCRP, fasting blood glucose and HOMA-IR of patients in the two groups preoperatively. But on the first postoperative day, fasting blood glucose and HOMA-IR of the patients in the study group were significantly lower than those in the control group (6.51±1.15vs7.49±0.57mmol/L, P=0.038;4.34±1.60vs6.09±2.81, P=0.043), and hsCRP level of the patients in the study group was significantly lower than the control group (40.45±27.02vs80.02±38.98mg/L, P=0.03). On the second postoperative day, hsCRP level of the patients in the study group was significantly lower than the control group(70.33±32.19vs101.12±42.73, P=0.041)Conclusion:Preoperative oral glucose solution(25%) is safe and feasible, obviously improved blood glucose and insulin resistance after operation, at the same time, alleviated postoperative inflammatory reaction. Part.4A clinical study of Laparoscopic bariatric surgery in treating modality for Background:Obesity has seriously affected the health and quality of life, become a important reason that induce the metabolic syndrome and complication of obesity. The recent10years studies show that the effect of conservative treatment on patients with severe obesity is limitied and bariatric surgery is the most effective method in weight control of morbid obesity patients. However, bariatric surgery is at the initial stage in China. There are many problems, such as the operation indication, unsatisfactory operation effect, the problem of postoperative complications and regain obesity, so there are still more research whcih need large sample, multi-center to confirm its effect. Obese patients accompany with multi-system problems, that need to multidisciplinary professional team to follow up and ensure the operation safety and effect. In order to standardize the process of treating obesity surgery in China, the Peking Union Medical College Hospital launched a model of multidisciplinary in treating morbid obese patients.Objective:To investigate the multidisciplinary modality for obesity treatment and evaluate the safety and long-term efficacy of laparoscopic adjustable gastric banding(LAGB) and laparoscopic sleeve gastrectomy(LSG) on weight loss, inflammation and obesity related metabolic diseases in obesity patients. Comparison effects of two kinds of bariatric surgeries provides the basis in the choice of mode of operation for the Chinese obese patients.Methods:The clinical and follow-up data of31and14morbidly obese patients, receiving LAGB and LSG respectively in Dept. General Surgery of PUMC hospitM in a multidisciplinary modality from Oct2009to March2014were retrospectively analyzed. The strategy of perioperative and follow-up management was summarized and the safety and long-term efficacy of LAGB and LSG on weight loss and comorbidity were evaluated.Results:All patients were successfully performed operation, without death case. Mean body weight of the subjects was121.7±22.5kg and mean BMI42.86±6.95kg/m2in LAGB group preoperatively, while mean body weight of the subjects was126.3±38.9kg and mean BMI43.57±10.21kg/m2in LSG group. All patients underwent LAGB and LSG successfully without perioperative mortality. Early postoperative complications included1case(3.2%) in LAGB of systemic inflammatory response syndrome and1case(7.1%) in LSG of incomplete obstruction. Long-term complications included2cases(6.5%) in LAGB of port infection and elevation. Mean body weight and BMI decreased gradually after LAGB and LSG. The mean percentage of excess weight loss(%EWL) at postoperative48months in LAGB group and12months in LSG group were48.0%and89.5%respectively. LSG was more effective in controling weight than LAGB at postoperative12months.%EWL of the group with regular follow-up and good compliance after LAGB was significantly higher than the other group. Complete or partial remission was observed in obesity related metabolic diseases at the last follow-up after LAGB and LSG.Conclusion:LAGB and LSG are safe and have good long-term efficacy on weight loss, reduce obesity-associated inflammation and improve comorbidity of morbidly obese patients. Better services can be provided for obesity patients in a muhidiseiplinaly modabty. It is important for the patients to follow up regularly after surgery in order to maintain long-term weight loss. LSG has a better effect on weight loss than LAGB...