Duodenal-jejunal bypass maintains hepatic S-adenosylmethionine/S-homocysteine ratio in diet-induced obese rats.

We previously reported that the duodenal-jejunal bypass (DJB) surgery altered transsulfuration and purine metabolism via flux changes in 1-carbon metabolism in the liver. In this study, we extended our study to gain further insight into mechanistic details of how the DJB-induced flux changes in 1-carbon metabolism contributes to the improvement of diet-induced nonalcoholic fatty liver disease. Rodents were subjected to surgical (sham operation and DJB) or dietary (reduced food supply to follow the weight changes in the DJB group) interventions. The microscopic features of the liver were examined by immunohistochemistry. The expressions of genes in lipid synthesis and in 1-carbon cycle in the liver were analyzed by real-time polymerase chain reaction and western blotting. Metabolic changes in the liver were determined. We observed that DJB reduces hepatic steatosis and improves insulin sensitivity in both high-fat diet-fed rats and mice. Metabolic analyses revealed that the possible underlying mechanism may involve decreased S-adenosylmethionine (SAM)-to-S-adenosylhomocysteine ratio via downregulation of SAM synthesizing enzyme and upregulation of SAM catabolizing enzyme. We also found in mice that DJB-mediated attenuation of hepatic steatosis is independent of weight loss. DJB also increased hepatic expression levels of GNMT while decreasing those of PEMT and BHMT, a change in 1-carbon metabolism that may decrease the ratio of SAM to S-adenosylhomocysteine, thereby resulting in the prevention of fat accumulation in the liver. Thus, we suggest that the change in 1-carbon metabolism, especially the SAM metabolism, may contribute to the improvement of diet-induced fatty liver disease after DJB surgery.

Duodenal-Jejunal Bypass Surgery Stimulates the Expressions of Hepatic Sirtuin1 and 3 and Hypothalamic Sirtuin1.

BACKGROUND: Sirtuins mediate metabolic responses to nutrient availability and slow aging and accompanying decline in health. This study was designed to assess the expressions of sirtuin1 (SIRT1) and sirtuin3 (SIRT3) in the liver and hypothalamus after duodenal-jejunal bypass (DJB) surgery in rats. METHODS: A total of 38 rats were randomly assigned to either sham group (n=8) or DJB group (n=30). DJB group was again divided into three groups according to the elapsed time after surgery (10 weeks, DJB10; 16 week, DJB16; 28 week, DJB28). The mRNA and protein expressions of SIRT1 and SIRT3 in the liver and hypothalamus were measured by reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry analyses. NAD+/NADH ratio was also measured. RESULTS: We found increased mRNA and protein expression levels of SIRT1 in the liver of DJB16 and DJB28 groups compared with those of sham group. The mRNA and protein expressions of SIRT3 in the liver of DJB group increased proportionally to the elapsed time after DJB surgery. The mRNA expression levels of SIRT1 in the hypothalamus increased in DJB16 and DJB28 groups and protein expression levels of SIRT1 in the hypothalamus increased in DJB10, DBJ16, and DJB28 groups compared with sham group. We observed that mRNA and protein levels of SIRT3 in the hypothalamus of DJB group were not changed. CONCLUSION: This study proves that DJB increases SIRT1 and SIRT3 expressions in the liver and SIRT1 expression in the hypothalamus. These results suggest the possibility of sirtuins being involved in bypass surgery-induced metabolic changes.

Cardiovascular Risk Factors in Gastric Cancer Patients Decrease 1 Year After Gastrectomy.

BACKGROUND: Due to the high 5-year overall survival rate (>95 %) for early gastric cancer (EGC), patients now face risks of developing comorbidities. Cardiovascular disease (CVD) is one of the most common causes of death not only in the general population and but also in cancer patients. Thus, we determined the effect of gastrectomy on cardiovascular risk factors by analyzing changes in lipid profiles of patients who underwent curative gastrectomy for EGC. METHODS: Seventy-three patients who received curative gastrectomy for EGC were included and divided into gastroduodenostomy (GD) and duodenal bypass (DB) groups according to the anastomosis. Changes in visceral fat area (VFA), subcutaneous fat area (SFA), and lipid profiles [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] were evaluated in both groups 1 year after gastrectomy. RESULTS: Body weight, VFA, SFA, TG, LDL-C, and TC decreased significantly while HDL-C increased (p < 0.001) after the surgery. We observed a weak negative correlation between percent change of VFA and HDL-C (r = -0.245, p = 0.036). When compared with the GD group, the DB group lost more SFA (p < 0.001), body weight (p = 0.008), and TC (p = 0.031). We also found that the degree of BMI change (∆BMI) was greater in the obese patients than in the non-obese patients (p < 0.001). CONCLUSIONS: Curative gastrectomy reduces VFA, SFA, and body weight and improves lipid profiles in patients with EGC, all of which indicates reduced cardiovascular risk. Therefore, prospective studies are required to verify whether gastrectomy in EGC patients has favorable effects on future CVD mortality.

Changes in Glucose Metabolism in Vertical Sleeve Gastrectomy.

BACKGROUND: We evaluated metabolic changes after vertical sleeve gastrectomy (VSG) surgery in a rat model using proteomics and metabolomic profiling in liver and serum. METHODS: Rats were randomly divided into two groups: sham (n = 10) and VSG (n = 12). Food intake, body weight, blood glucose, insulin, and thyroid hormone levels were measured. Two-dimensional electrophoresis, nuclear resonance spectroscopy, mass spectroscopy, immunofluorescence, and immunoblot analyses were used to determine and validate changes in metabolites and proteins in liver tissue and serum samples. RESULTS: Food intake and body weight decreased after VSG group (p < 0.05 and p < 0.05, respectively). Random blood glucose (sham, 183.3 ± 5.6 mg/dL; VSG, 138.5 ± 3.7 mg/dL) decreased while random insulin (sham, 0.45 ± 0.16 µg/L; VSG, 1.05 ± 0.18 µg/L) increased after VSG (p < 0.05 and p < 0.01, respectively). We found that expressions of gluconeogenic enzymes (phosphoenolpyruvate carboxykinase-1 and glucose-6-phosphatase) and concentrations of pyruvate and malate decreased while lactate, NADH, NADPH, glucose, and AMP/ATP ratio increased after VSG. Thyroid hormones, triiodothyronine (T3) and free thyroxine (fT4), decreased after VSG. CONCLUSION: This study proves that VSG suppresses hepatic glucose production.

Effect of normal saline irrigation on attenuation of shoulder tip pain and on ß-endorphin levels after laparoscopic cholecystectomy.

AIM: The purpose of this study was to evaluate the effect of saline washout under the diaphragm on postoperative shoulder tip pain (STP) and ß-endorphin (ßE) levels in patients who had undergone laparoscopic cholecystectomy (LC). METHODS: Between December 2010 and March 2011, 50 patients requiring cholecystectomy for benign gallbladder disease were enrolled in this study. Twenty-five patients (Group 1) underwent LC without saline irrigation, whereas the other 25 were operated on with saline irrigation (30 mL/kg) under the diaphragm (Group 2). Plasma levels of ßE were measured before and after the operation. The degree of STP following LC was assessed using a visual analog pain scale (VAS) at 6, 12, and 24 hours postoperatively. RESULTS: Eight patients in Group 1 (32.0%) and seven patients in Group 2 (28.0%) complained of STP. There was no significant difference between the two groups in operation time, postoperative hospital length, postoperative ßE, dose of analgesics, or VAS at 6, 12, and 24 hours after surgery. The intensity of abdominal pain (AP) was significantly higher than that of STP. Significantly elevated levels (11.3±5.1 pg/mL) of ßE were observed postoperatively when compared with preoperative levels (9.7±5.2 pg/mL) (P=.02). CONCLUSIONS: Normal saline irrigation under the diaphragm does not reduce postoperative STP after LC. Ancillary techniques to reduce AP and STP should be considered.