An increase in gastroesophageal reflux disease (GERD) after laparoscopic sleeve gastrectomy (LSG) has been reported, and concomitant hiatal hernia repair (HHR) during LSG is expected to reduce the incidence of post-LSG GERD. In HHR, the hepatic branch of the vagus nerve is anatomically transected. Recent experimental animal models suggest that vagotomy may affect glycemic control and weight loss through a neuroendocrine response.

To examine whether LSG with/without hepatic branch vagotomy (HV) has a clinical impact on glycemic control in patients with obesity and type 2 diabetes mellitus (T2DM). Furthermore, the impact on weight loss and post-LSG GERD were evaluated.

A total of 204 Japanese patients with obesity and T2DM, who underwent LSG and completed 1-year follow-up, were retrospectively analyzed. Operative outcomes, weight loss, glycemic, and GERD-related parameters were compared between the LSG/HHR/HV group (n = 89) and the LSG group (n = 115).

There was no significant difference in the background factors in terms of anthropometric and T2DM-related parameters between the groups. The median operation times in the LSG/HHR/HV and LSG groups were 133 and 124 minutes, respectively (p = 0.236). At 1 year, the diabetes remission rate, HbA1c, fasting glucose, and C-peptide levels were all comparable between the groups. The weight loss effect was also comparable. The patients in the LSG/HHR/HV group achieved significant improvement and prevention of GERD and hiatus hernia (p < 0.001).

HV does not appear to have a clinical impact on glycemic control and weight loss. Concomitant HHR with LSG serves to reduce post-LSG GERD.

Bariatric surgery is often performed not only to lose weight, but also to improve obesity-related comorbidities. A certain metabolic effect of the bariatric techniques has been demonstrated, as the improvement or even remission of comorbidities is patent, before having lost a relevant amount of weight. The autonomic innervation of diverse viscera by the vagus nerve has been hypothesized to participate in it. We aimed to evaluate the ponderal and metabolic impact of the preservation of the hepatic branch of the vagus in type 2 diabetic (T2D) patients undergoing one-anastomosis gastric bypass (OAGB).

We conducted a prospective study on patients with a preoperative diagnosis of morbid obesity and T2D, who underwent an OAGB. Preservation of the hepatic branch of the vagus was carried out in the first 14 patients (Group 1), whereas in another 14 patients it was sectioned. Ponderal and metabolic outcomes were assessed 1 and 2 years after surgery.

The length of the biliary limb was 210 cm in both groups. Postoperative BMI or excess BMI loss was not significantly different between groups. The patients included in Group 1 showed a statistically greater improvement in glycemic and lipid variables.

The preservation of the hepatic branch of the vagus in an OAGB leads to more favorable postoperative glycemic and lipid profiles.

Our aim was to investigate the effects of selective celiac branch vagotomy on food intake and glycemic control after ileal transposition (IT) and the possible roles of the vagus on the improvement of diabetes.

Forty non-obese rats with diabetes underwent either IT, IT + celiac branch vagotomy (ITV), sham IT (SI), or sham IT + celiac branch vagotomy (SIV). They were pair fed, and the food intake, body weight, fasting plasma glucose, and glucagon-like peptide 1 (GLP-1) level were monitored. The number of activated pro-opiomelanocortin (POMC) neurons and POMC-derived peptides were measured after sacrifice.

The fasting glucose level of the ITV group was higher (7.0 ± 0.7 mmol/L vs. 5.7 ± 0.3, P = 0.01), and the area under the curve of the oral glucose tolerance test (AUCOGTT) value was greater than that of the IT group (1101.8 ± 90.3 (mmol/l) min vs. 986.9 ± 47.7 (mmol/l) min, P = 0.01). There was no significant difference in the postprandial GLP-1 level between these two groups, but the number of activated neurons in the ITV group was less than that of the IT group (10.3 ± 2.1 vs. 14.9 ± 2.3, P < 0.01), while the relative content level of POMC-derived peptides in the ITV group was half that of the IT group (P < 0.01).

The celiac branches of the vagus might contribute to less eating and improvement of diabetes after IT. The activating vagus strategy might be a goal for the treatment of diabetes.

Animal models are widely used to develop drugs for treating diabetes mellitus (DM). Insulin resistance (IR) is one of the main problems in type-2 DM (T2DM). Streptozotocin (STZ) is used to damage pancreatic cells for induction of DM. Many rat models were applied in research as T2DM. However, the degree of IR in each model is unknown. In the present study, IR and insulin signaling were compared in four models of type 2 diabetes: rats fed a fructose-rich chow for 8 weeks, rats feed high-fat chow for 4 weeks followed by injection with streptozotocin (35 mg/kg, i.p.), rats injected with a single low dose streptozotocin (45 mg/kg, i.p.), and rats injected with a single dose of nicotinamide followed by a single high dose of streptozotocin (60 mg/kg, i.p.). Values from these determinations in diabetic rats showing the order that insulin resistance is most marked in rats received fructose-rich chow followed by high-fat diet before STZ injection induced model (HFD/STZ rats), and rats injected with low dose of STZ but it is less marked in rats induced by nicotinamide and STZ. Additionally, insulin secretion was reduced in three rat models except the rats receiving fructose-rich chow. Western blots also showed the same changes in phosphorylation of IRS-1 or Akt using soleus muscle from each model. The obtained data suggest a lack of pronounced IR in the rats with acute diabetes induced by nicotinamide and STZ while IR is markedly identified in rats fed fructose-rich chow. However, the increase of plasma glucose levels in fructose-rich chow-fed rats was not so significant as other groups. Therefore, HFD/STZ rats is an appropriate and stable animal model which is analogous to the human T2DM through a combination of high-fat diet with multiple low-dose STZ injections.

Postprandial hypoglycemia is an infrequent but disabling complication of Roux-en-Y gastric bypass (RYGB) surgery. Controversy still exists as to whether the postprandial hyperinsulinemia observed is due to inherent changes in pancreatic β-cell mass or function or to reversible alterations caused by RYGB anatomy. We aimed to determine if gastric feeding or reversal of RYGB would normalize postprandial glucose and hormone excursions in patients with symptomatic hypoglycemia.

We completed a prospective study of six patients with severe symptomatic RYGB hypoglycemia who underwent RYGB reversal. An additional subject without hypoglycemia who underwent RYGB reversal was also studied prospectively. Mixed meal tolerance testing (MTT) was done orally (RYGB anatomy), via gastrostomy tube in the excluded stomach in the setting of RYGB, and several months after RYGB reversal.

All subjects reported symptomatic improvement of hypoglycemia after reversal of RYGB. Weight gain after reversal was moderate and variable. Postprandial glucose, insulin, and GLP-1 excursions were significantly diminished with gastric feeding and after reversal. Insulin secretion changed proportional to glucose levels and insulin clearance increased after reversal. Glucagon/insulin ratios were similar throughout study. We further compared the impact of modified sleeve gastrectomy reversal surgery to those with restoration of complete stomach and found no significant differences in weight regain or in postprandial glucose or hormone levels.

Reversal of RYGB is an effective treatment option for severe postprandial hypoglycemia. The pathophysiology of this disorder is primarily due to RYGB anatomy resulting in altered glucose, gut, and pancreatic hormone levels and decreased insulin clearance, rather than inherent β-cell hyperplasia or hyperfunction.

Obesity has reached epidemic proportions and, to date, bariatric surgery remains the only effective treatment for morbid obesity in terms of its capacity to achieve durable weight loss. Bariatric surgery procedures, including Roux-en-Y gastric bypass (RYGB), adjustable gastric banding (AGB) and sleeve gastrectomy (SG), have been the primary procedures conducted over the past decade, with SG increasing in popularity over the past 5 years at the expense of both RYGB and AGB. Although these procedures were initially proposed to function via restrictive or malabsorptive mechanisms, it is now clear that profound physiological changes underlie the metabolic improvements in patients who undergo bariatric surgery. Data generated in human patients and animal models highlight the rapid and sustained changes in gut hormones that coincide with these procedures. Furthermore, recent studies highlight the involvement of the nervous system, specifically the vagus nerve, in mediating the reduction in appetite and food intake following bariatric surgery. What is unclear is where these pathways converge and interact within the gut-brain axis and whether vagally-mediated circuits are sufficient to drive the metabolic sequalae following bariatric surgery.

To examine the changes of the ghrelin/ghrelin O-acyltransferase (GOAT) axis and the mammalian target of rapamycin (mTOR) pathway in the hypothalamus after sleeve gastrectomy.

A total of 30 obese type-2 diabetes Sprague-Dawley (SD) rats, 6 wk of age, fed with high-sugar and high-fat fodder for 2 mo plus intraperitoneal injection of streptozotocin were randomly divided into three groups: non-operation group (S0 group, n = 10), sham operation group (Sh group, n = 10) and sleeve gastrectomy group (SG group, n = 10). Data of body mass, food intake, oral glucose tolerance test (OGTT), acylated ghrelin (AG) and total ghrelin (TG) were collected and measured at the first day (when the rats were 6 wk old), preoperative day 3 and postoperative week 8. The mRNA expression of preproghrelin, GOAT and neuropeptide Y (NPY), and protein expression of ghrelin, GOAT, GHSR and the mTOR pathway (p-Akt, p-mTOR and p-S6) were measured in the hypothalamus.

SG can significantly improve metabolic symptoms by reducing body mass and food intake. The obese rats showed lower serum TG levels and no change in AG, but the ratio of AG/TG was increased. When compared with the S0 and Sh groups, the SG group showed decreased TG (1482.03 ± 26.55, 1481.49 ± 23.30 and 1206.63 ± 52.02 ng/L, respectively, P < 0.05), but unchanged AG (153.06 ± 13.74, 155.37 ± 19.30 and 144.44 ± 16.689 ng/L, respectively, P > 0.05). As a result, the ratio of AG/TG further increased in the SG group (0.103 ± 0.009, 0.105 ± 0.013 and 0.12 ± 0.016, respectively, P < 0.05). When compared with the S0 group, SG suppressed mRNA and protein levels of preproghrelin (0.63 ± 0.12 vs 0.5 ± 0.11, P < 0.05) and GOAT (0.96 ± 0.09 vs 0.87 ± 0.08, P < 0.05), but did not change NPY mRNA expression (0.61 ± 0.04 vs 0.65 ± 0.07, P > 0.05) in the hypothalamus. The protein levels of p-Akt, p-mTOR and p-S6 were higher in the SG group, which indicated that the hypothalamic mTOR pathway was activated after SG at the postoperative week 8.

The reduction of ghrelin expression and activation of the mTOR pathway might have opposite effects on food intake, as SG improves obesity and T2DM.

Vagus nerve may play a role in serum glucose modulation. The complicated peptic ulcer patients (with perforation or/and bleeding) who received surgical procedures with or without vagotomy provided 2 patient populations for studying the impact of vagus nerve integrity. We assessed the risk of developing type 2 diabetes in peptic ulcer patients without and with complications by surgical treatment received in a retrospective population study using the National Health Insurance database in Taiwan.A cohort of 163,385 patients with peptic ulcer and without Helicobacter pylori infection in 2000 to 2003 was established. A randomly selected cohort of 163,385 persons without peptic ulcer matched by age, sex, hypertension, hyperlipidemia, Charlson comorbidity index score, and index year was utilized for comparison. The risks of developing diabetes in both cohorts and in the complicated peptic ulcer patients who received truncal vagotomy or simple suture/hemostasis (SSH) were assessed at the end of 2011.The overall diabetes incidence was higher in patients with peptic ulcer than those without peptic ulcer (15.87 vs 12.60 per 1000 person-years) by an adjusted hazard ratio (aHR) of 1.43 (95% confidence interval [CI] = 1.40-1.47) based on the multivariable Cox proportional hazards regression analysis (competing risk). Comparing ulcer patients with truncal vagotomy and SSH or those without surgical treatment, the aHR was the lowest in the vagotomy group (0.48, 95% CI = 0.41-0.56).Peptic ulcer patients have an elevated risk of developing type 2 diabetes. Moreover, there were associations of vagus nerve severance and decreased risk of subsequent type 2 diabetes in complicated peptic ulcer patients.

Vagal afferent neurons (VANs) play an important role in the control of food intake by signaling nutrient type and quantity to the brain. Recent findings are broadening our view of how VANs impact not only food intake but also energy homeostasis. This review focuses exclusively on studies of the vagus nerve from the past 2 years that highlight major new advancements in the field. We firstly discuss evidence that VANs can directly sense nutrients, and we consider new insights into mechanisms affecting sensing of gastric distension and signaling by gastrointestinal hormones ghrelin and GLP1. We discuss evidence that disrupting vagal afferent signaling increases long-term control of food intake and body weight management, and the importance of this gut-brain pathway in mediating beneficial effects of bariatric surgery. We conclude by highlighting novel roles for vagal afferent neurons in circadian rhythm, thermogenesis, and reward that may provide insight into mechanisms by which VAN nutrient sensing controls long-term control of energy homeostasis.