Sleeve gastrectomy decreases high-fat diet induced colonic pro-inflammatory status through the gut microbiota alterations.

Background: High-fat diet (HFD) induced obesity is characterized with chronic low-grade inflammation in various tissues and organs among which colon is the first to display pro-inflammatory features associated with alterations of the gut microbiota. Sleeve gastrectomy (SG) is currently one of the most effective treatments for obesity. Although studies reveal that SG results in decreased levels of inflammation in multiple tissues such as liver and adipose tissues, the effects of surgery on obesity related pro-inflammatory status in the colon and its relation to the microbial changes remain unknown. Methods: To determine the effects of SG on the colonic pro-inflammatory condition and the gut microbiota, SG was performed on HFD-induced obese mice. To probe the causal relationship between alterations of the gut microbiota and improvements of pro-inflammatory status in the colon following SG, we applied broad-spectrum antibiotics cocktails on mice that received SG to disturb the gut microbial changes. The pro-inflammatory shifts in the colon were assessed based on morphology, macrophage infiltration and expressions of a variety of cytokine genes and tight junction protein genes. The gut microbiota alterations were analyzed using 16s rRNA sequencing. RNA sequencing of colon was conducted to further explore the role of the gut microbiota in amelioration of colonic pro-inflammation following SG at a transcriptional level. Results: Although SG did not lead to pronounced changes of colonic morphology and macrophage infiltration in the colon, there were significant decreases in the expressions of several pro-inflammatory cytokines including interleukin-1ß (IL-1ß), IL-6, IL-18, and IL-23 as well as increased expressions of some tight junction proteins in the colon following SG, suggesting an improvement of pro-inflammatory status. This was accompanied by changing populations of the gut microbiota such as increased richness of Lactobacillus subspecies following SG. Importantly, oral administrations of broad-spectrum antibiotics to delete most intestinal bacteria abrogated surgical effects to relieve colonic pro-inflammation. This was further confirmed by transcriptional analysis of colon indicating that SG regulated inflammation related pathways in a manner that was gut microbiota relevant. Conclusion: These results support that SG decreases obesity related colonic pro-inflammatory status through the gut microbial alterations.

Lipid Profiling Reveals Lipidomic Signatures of Weight Loss Interventions.

Obesity is an epidemic all around the world. Weight loss interventions that are effective differ from each other with regard to various lipidomic responses. Here, we aimed to find lipidomic biomarkers that are related to beneficial changes in weight loss. We adopted an untargeted liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to measure 953 lipid species for Exercise (exercise intervention cohort, N = 25), 1388 lipid species for LSG (laparoscopic sleeve gastrectomy cohort, N = 36), and 886 lipid species for Cushing (surgical removal of the ACTH-secreting pituitary adenomas cohort, N = 25). Overall, the total diacylglycerol (DG), triacylglycerol (TG), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM) levels were associated with changes in BMI, glycated hemoglobin (HbA1c), triglyceride, and total cholesterol according to weight loss interventions. We found that 73 lipid species changed among the three weight loss interventions. We screened 13 lipid species with better predictive accuracy in diagnosing weight loss situations in either Exercise, LSG, or Cushing cohorts (AUROC > 0.7). More importantly, we identified three phosphatidylcholine (PC) lipid species, PC (14:0_18:3), PC (31:1), and PC (32:2) that were significantly associated with weight change in three studies. Our results highlight potential lipidomic biomarkers that, in the future, could be used in personalized approaches involving weight loss interventions.

Sleeve gastrectomy improved microvascular phenotypes from obesity cohort, detected with optical coherence tomography angiography.

AIMS: To examine how metabolic status is associated with microvascular phenotype and to identify variables associated with vascular remodeling after bariatric surgery, using noninvasive optical coherence tomography angiography (OCTA). METHODS: The study included 136 obese subjects scheduled for bariatric surgery and 52 normal-weight controls. Patients with obesity were divided into metabolically healthy obesity (MHO) and metabolic syndrome (MetS) groups according to the diagnosis criteria of the Chinese Diabetes Society. Retinal microvascular parameters were measured by OCTA, including superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel densities. Follow-ups were performed at the baseline and 6 months after bariatric surgery. RESULTS: Fovea SCP, average DCP, fovea DCP, parafovea DCP, and perifovea DCP vessel densities were significantly lower in the MetS group, compared to controls (19.91% vs. 22.49%, 51.60% vs. 54.20%, 36.64% vs. 39.14%, 56.24% vs. 57.65% and 52.59% vs. 55.58%, respectively, all p < .05). Parafovea SCP, average DCP, parafovea DCP, and perifovea DCP vessel densities significantly improved in patients with obesity 6 months after surgery, compared to baseline (54.21% vs. 52.97%, 54.43% vs. 50.95%, 58.29% vs. 55.54% and 55.76% vs. 51.82%, respectively, all p < .05). Multivariable analyses showed that baseline blood pressure and insulin were independent predictors of vessel density changes 6 months after surgery. CONCLUSIONS: Retinal microvascular impairment occurred mainly in MetS rather than MHO patients. Retinal microvascular phenotype improved 6 months after bariatric surgery and baseline blood pressure and insulin status may be key determinants. OCTA may be a reliable method to evaluate the microvascular complications associated with obesity.

Sleeve gastrectomy ameliorated high-fat diet (HFD)-induced non-alcoholic fatty liver disease and upregulated the nicotinamide adenine dinucleotide +/ Sirtuin-1 pathway in mice.

BACKGROUND: /Objective: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, and effective treatments are lacking. Bariatric surgery, including sleeve gastrectomy (SG), is a potential therapeutic strategy for NAFLD, but the molecular mechanisms underlying its effects are not fully understood. In this study, the effects of SG and the underlying mechanisms were evaluated in a mouse model of high-fat diet (HFD)-induced NAFLD. METHODS: C57BL/6 mice were randomly divided into three groups: normal diet with sham operation (NC-Sham group), HFD with sham operation (HFD-Sham group), and HFD with sleeve gastrectomy (HFD-SG group). Glucose metabolism and fat accumulation in the body and liver were analyzed before and after SG. Lipid metabolism and inflammation in the liver were evaluated. Nicotinamide adenine dinucleotide (NAD+) levels as well as nicotinamide riboside kinase (NRK1) and Sirtuin-1 (SIRT1) expression levels were evaluated. RESULTS: SG attenuated the HFD-induced increases in glucose and insulin levels, fat accumulation, and lipid droplet accumulation. Fatty acid biosynthesis, the expression of the metabolism-related genes ACC1, FASN, SCD1, and DGAT1, and the levels of inflammatory factors were higher in HFD mice than in NC mice and decreased after SG. NAD + concentrations were 54.9 ± 13.4 µmol/mg in NC-Sham mice, 37.6 ± 8.1 µmol/mg in HFD-Sham mice, and 79.9 ± 13.0 µmol/mg in HFD-SG mice (p < 0.05). NRK1 and SIRT1 expression increased dramatically after SG at both the RNA and protein levels. CONCLUSION: SG significantly alleviated NAFLD in HFD-induced obese mice with increasing the hepatic NAD + levels and upregulating the NRK1/NAD+/SIRT1 pathway.

A Qualitative Exploration of Patients' Experiences with Lifestyle Changes After Sleeve Gastrectomy in China.

PURPOSE: Sleeve gastrectomy (SG) is the most widely used surgical treatment for severe obesity worldwide. Individuals who have undergone SG usually need to change lifestyle behaviors as a response to the anatomical changes imposed by SG, and patients need to sustain lifestyle changes for long-term surgical success. Little is known about how patients experience and manage lifestyle changes following SG. In China, where SG comprises over 70% of bariatric surgical procedures, there have been no reports addressing this issue. This study aimed to describe individuals' experiences related to lifestyle changes after SG in China. MATERIALS AND METHODS: Semi-structured interviews were conducted at the Shanghai Huashan Hospital in China with adults who had undergone SG between 2012 and 2018. Two independent researchers used an interpretive thematic approach to analyze transcripts for themes and sub-themes. RESULTS: Interviews (N = 15) revealed three major themes of participants' experiences with postoperative lifestyle changes: advantages outweigh disadvantages; developing self-management strategies (i.e., adopting new behaviors and developing habits, continuing self-monitoring, focusing on health over weight, staying determined); and experiencing culture-specific difficulties in adherence to follow-up visits and lifestyle recommendations. CONCLUSION: The data from this study provided a rich description of the postoperative experiences of patients in China. Participants reported that surgical benefits supersede the surgery-related side effects, and participants were able to develop self-management strategies in order to achieve success. However, personal and social barriers, such as the challenges of applying postoperative dietary guidelines into daily practice, may impede patients making and sustaining recommended behavioral changes.

Prevalence and risk factors for symptoms suggestive of hypoglycemia and early dumping syndrome after sleeve gastrectomy.

BACKGROUND: Postprandial hypoglycemia and early dumping syndrome are common complications after bariatric surgery. Although sleeve gastrectomy (SG) has become a primary option for many bariatric surgeons, limited information was available for the prevalence and risk factors of the complications. OBJECTIVE: To assess the prevalence and possible risk factors for postprandial hypoglycemia and early dumping syndrome based on self-reported symptoms of SG patients. SETTING: The study was conducted at a bariatric surgery center in a university hospital. METHODS: In this study, all patients who underwent an SG (n = 222) between December 2011 and May 2018 in our center were invited to participate in a questionnaire survey. The Edinburgh Hypoglycemia Scoring System and the Dumping Symptom Rating Scale were used to evaluate symptoms, and clinical data of the patients were collected. The median follow-up time was 1.1 years. RESULTS: The questionnaire was completed and returned by 54.95% (122/222) of the patients and 62.30% (76/122) of the responders were women. The prevalence rates of mild and moderate symptoms suggestive of hypoglycemia were 65.57% (80/122) and .82%, respectively. An associated risk factor was younger age (adjusted for sex, body mass index, and waist circumference at baseline: odds ratio 3.69; 95% confidence interval [1.22-11.21]), but this association disappeared after further adjustment of low-density protein cholesterol (LDL-C) (odds ratio 6.42; 95% confidence interval [.38-108],;P > .05). The prevalence rate of mild symptoms suggestive of early dumping was 40.98% (50/122), associated risk factor was lower LDL-C. CONCLUSION: Mild-to-moderate symptoms suggestive of hypoglycemia and early dumping syndrome were common in patients after SG, with the prevalence rates of 66.39% (81/122) and 40.98% (50/122), respectively. Patients with both symptoms suggestive of early dumping syndrome and hypoglycemia accounted for 33.61% (41/122) of all patients. Younger age indicated higher risk of hypoglycemia after SG and lower LDL-C may play an important role in this relationship. Lower LDL-C was associated with higher risk of early dumping syndrome after SG.

Pb exposure reduces the expression of SNX6 and Homer1 in offspring rats and PC12 cells.

Lead (Pb) is a widespread environmental heavy metal toxicant and chronic Pb exposure can have irreversible effects on memory and cognitive function, which is closely related to dendritic spines. Studies have shown that SNX6 and Homer1 can regulate the growth of dendritic spines. We aimed to investigate the effect of Pb exposure on the dendritic spines in hippocampus, the expression of SNX6 and Homer1 in rats and PC12 cells. The animals were randomly divided to three groups: control group, low lead group and high lead group. PC12 cells were divided into 3 groups: 0 µM, 1 µM and 100 µM Pb acetate. The results showed that the Pb levels in blood and hippocampus of all exposure groups were significantly higher than that of the control group. The morphology of dendritic spines in hippocampus after Pb treatment was changed and the density of dendritic spines was reduced. The expression of SNX6 and Homer1 was decreased in Pb exposed groups compared with the control group. Furthermore, up-regulation of SNX6 expression could reverse the down-regulation of Pb exposure on Homer1. These results indicate that Pb exposure can reduce the expression of SNX6 and lead to a decrease in Homer1 expression, which affects the changes in dendritic spines causing learning and memory impairment.

Effects of sleeve gastrectomy on the composition and diurnal oscillation of gut microbiota related to the metabolic improvements.

BACKGROUND: Disruptions of the composition and diurnal oscillation of gut microbiota are involved in metabolic disorders. OBJECTIVES: To identify alterations in both the composition and diurnal oscillation of gut microbiota after high-fat diet (HFD) feeding and sleeve gastrectomy (SG) related to host metabolic status. SETTING: University laboratories. METHODS: Twenty-one 6-week-old male C57 BL/6 J mice were randomized on an HFD (n = 14) or normal chow (NC, n = 7). After 14 weeks of feeding, HFD-induced obese mice were randomized to receive either SG or sham surgery (n = 7 in each group). Fecal samples were collected every 6 hours over a 24-hour period at 14 weeks of NC or HFD feeding and subsequently 8 weeks after surgery. The composition and diurnal oscillation of gut microbiota were characterized using next-generation Illumina sequencing of 16 S rDNA. RESULTS: HFD feeding led to adiposity, disrupted composition, and impaired diurnal oscillation of gut microbiota relative to NC. After surgery, SG mice had considerable weight loss, improved glucose tolerance, and insulin sensitivity compared with sham mice. SG restored the reduced richness and disruptions in the composition of gut microbiota. The diminished diurnal oscillation of gut microbiota was improved after SG. CONCLUSION: SG not only changed the disrupted composition of gut microbiota toward that of NC feeding, but also improved the dampened diurnal oscillation of gut microbiota due to HFD feeding.

The effects of lead exposure on the expression of HMGB1 and HO-1 in rats and PC12 cells.

Lead (Pb) is an environmental neurotoxic metal. Chronic exposure to Pb causes deficits of learning and memory in children and spatial learning deficits in developing rats. In this study we investigated the effects of Pb exposure on the expression of HMGB1 and HO-1 in rats and PC12 cells. The animals were randomly divided to three groups: control group; low lead exposure group; high lead exposure group; PC12 cells were divided into 3 groups: 0 µM (control group), 1 µM and 100 µM Pb acetate. The results showed that Pb levels in blood and brain of Pb exposed groups were significantly higher than that of the control group (p < 0.05). The expression of HMGB1 and HO-1 were increased in Pb exposed groups than that of the control group (p < 0.05). Moreover, we found that the up-regulation of HO-1 in Pb exposure environment inhibited the expression of HMGB1.

MiR-145 improves macrophage-mediated inflammation through targeting Arf6.

PURPOSE: To explore the relationship between miR-145 and ADP ribosylation factor 6 (Arf6) in regulating macrophage-mediated inflammation. METHODS: THP-1 cells were induced by 160 nM of phorbol 12-myristate 13-acetate (PMA) for 48 h to differentiate to macrophages and then were treated with LPS (100 ng/ml) for 8 h to simulate chronic metabolic inflammation in vitro. Dual-luciferase reporter assay was performed. MiR-145 siRNA and LV-ARF6-RNAi were used to up or down regulate miR-145 and Arf6 expression in THP-1 cells, respectively. Omental adipose tissue from patients in surgical ward were collected to detect the expression of miR-145, Arf6 and production of proinflammatory cytokines. Patients were divided into three groups according to their body mass index and history of diabetes. RESULTS: Dual-luciferase reporter assays showed the direct down-regulation of Arf6 by miR-145. Forty-eight-hour-transfection of miR-145 inhibitor resulted in significant increase of Arf6, IL-1beta, TNF-alpha and IL-6 as well as phosphorylation of p65 in NF-kappaB pathway in THP-1 cells, which, inversely, were reversed by overexpressing miR-145. In addition, down-regulation of Arf6 in macrophages reduced expression and secretion of cytokines. Expression of miR-145 was found to be attenuated in the omental adipose tissue of obese patients and diabetics with greater Arf6 expression, confirming the role of miR-145 in regulating macrophage-mediated inflammation targeting Arf6. CONCLUSIONS: By means of reducing the expression of Arf6 and subsequent signal transduction via NF-kappaB, miR-145 plays a role in inhibiting the secretion of inflammatory factors and then improving the inflammatory status. MiR-145 might be one of the candidates for anti-inflammatory treatment for metabolic diseases.

Alterations of Gut Microbiota After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy in Sprague-Dawley Rats.

BACKGROUND: The objective of the study was to compare gut microbiota post Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). METHODS: Sprague-Dawley rats were randomized to RYGB, SG, or sham surgery. Body weight was measured. Fecal samples were collected before and 1, 3, 6, and 9 weeks postoperatively. Fecal microbiota was profiled by 16S ribosomal DNA gene sequencing and analyzed using Quantitative Insights into Microbial Ecology (QIIME) to determine the α and ß diversities of gut microbiota. RESULTS: The body weight of the RYGB and SG group was significantly lower than that of the sham group. Unweighted UniFrac-based principal coordinate analysis of 5,323,091 sequences from 85 fecal samples from 17 rats revealed a distinct cluster of gut microbiota post RYGB from SG and sham surgery. The percentage of Proteobacteria in the SG and sham group remained markedly lower than that of the RYGB group from 3 weeks postoperatively, while the proportion of Gammaproteobacteria in the RYGB group was significantly higher than that of the SG group and the sham group from 3 weeks postoperatively. Furthermore, the RYGB group was postoperatively enriched for Gammaproteobacteria and Bacteroidaceae, whereas the SG group was postoperatively enriched for Desulfovibrionaceae and Cyanobacteria. Compared to the pre-operative parameters, the RYGB group had a persistent increase in the relative abundance of Gammaproteobacteria and a decrease in the Shannon index, while the SG group only transiently exhibited these changes within the first week after surgery. The relative abundance of Gammaproteobacteria was negatively correlated, whereas the Shannon index was positively correlated with weight after surgery. CONCLUSIONS: RYGB, but not SG, alters the gut microbiota of Sprague-Dawley rats. RYGB also reduces the diversity of gut microbiota. Furthermore, the abundance of Gammaproteobacteria negatively correlates with postoperative body weight and may be one of the potential contributors to stable weight loss after bariatric surgery.

Laparoscopic hernioplasty of hiatal hernia.

Laparoscopic surgery is a good choice for surgical treatment of hiatal hernia because of its mini-invasive nature and intraperitoneal view and operating angle. This article will talk about the surgical procedures, technical details, precautions and complications about laparoscopic hernioplasty of hiatal hernia.

A Comparative Study of the Effect of Gastric Bypass, Sleeve Gastrectomy, and Duodenal-Jejunal Bypass on Type-2 Diabetes in non-Obese Rats.

BACKGROUND: We compared the therapeutic effects of Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and duodenal-jejunal bypass (DJB) on type-2 diabetes mellitus (T2DM) in non-obese rats using clamp testing. METHODS: Goto-Kakizaki rats (non-obese rats with T2DM) underwent surgery: RYGB, SG, or DJB. Rats were observed for 8 weeks after surgery to evaluate weight changes. Levels of glucose, insulin, and glucagon-like peptide (GLP)-1 were determined 2, 4, 6, and 8 weeks after surgery. An oral glucose tolerance test (OGTT) and clamp test was used to evaluate glucose tolerance and insulin resistance. RESULTS: Rats in RYGB, SG, and DJB groups weighed significantly less than sham-group rats 6 and 8 weeks after surgery. Fasting blood glucose levels of RYGB, SG, and DJB rats were significantly lower than preoperative levels. One month after surgery, the area under the curve of the OGTT (in mmol•h/L) for RYGB, SG, DJB, and sham surgery groups was 38.9 ± 5.9, 50.9 ± 2.9, 46.8 ± 3.3, and 67.4 ± 6.0, respectively; there was no significant difference in glucose levels of SG and DJB groups. Glucose infusion rates (in mg/(kg•min)) were 18.3 ± 2.7, 17.2 ± 2.1, and 16.8 ± 1.9 in hyperinsulinemic-euglycemic-clamped RYGB, DJB, and SG rats, respectively, 8 weeks after surgery. The rate in the sham surgery group was 6.3 ± 0.9. Area under plasma insulin curves 8 weeks after surgery in hyperglycemic-clamped RYGB, DJB, SG, and sham surgery rats (in mU•h/L) were 98.8 ± 7.0, 84.4 ± 6.1, 89.0 ± 7.1, and 22.6 ± 2.6, respectively. CONCLUSIONS: The three surgical methods described alleviated T2DM and reduced insulin resistance in non-obese rats with T2DM.

Total fat consumption and pancreatic cancer risk: a meta-analysis of epidemiologic studies.

Fat consumption has been hypothesized to influence pancreatic cancer risk, but the results of epidemiologic studies have been controversial. We conducted a systematic review and meta-analysis of case-control and cohort studies to investigate this issue. Relevant published studies were identified by searching MEDLINE (PubMed) through February 2014. Two authors (Q.-W.S. and Q.-Y.Y.) independently assessed eligibility and the extracted data. Study-specific relative risks (RRs) were pooled using a random-effects model. We also carried out heterogeneity and publication bias analyses. Six cohort and 13 case-control studies with 6159 pancreatic cancer cases and 1,068,476 noncases were included in this meta-analysis. The summary RR for pancreatic cancer for the highest versus lowest intake was 1.04 [95% confidence interval (CI)=0.90-1.20, I²=57.3%, P for heterogeneity=0.001] for total fat. In addition, when separately analyzed by study design, case-control (RR=1.03, 95% CI=0.83-1.27, I²=55.8%, P for heterogeneity=0.007) and cohort studies (RR=1.05, 95% CI=0.85-1.29, I²=66.7%, P for heterogeneity=0.010) yielded similar results. Furthermore, no statistically significant associations were observed in the subgroup analyses on the basis of fat source, geographic location, whether using energy-adjusted models, and whether adjusted for several potential confounders and important risk factors. There was no evidence of publication bias or significant heterogeneity between subgroups on meta-regression analyses. The results of this meta-analysis do not support an independent association between diets high in total fat and pancreatic cancer risk.