Alcohol Misuse post Metabolic and Bariatric Surgery: A Systematic Review of Longer-term Studies with Focus on new Onset Alcohol use Disorder and Differences Between Surgery Types.

BACKGROUND: Evidence suggests an increased risk of alcohol problems post-surgery where no problematic alcohol use was present prior to surgery which may be different across types of surgery. OBJECTIVE: To characterise the risk of new onset alcohol misuse post bariatric surgery, differences between surgeries and the impact over time. METHODS: All published studies on new and relapsing alcohol use were reviewed. Data were classed as 'subjective' (clinical interview, self-report questionnaires) and 'objective' (hospital admissions, substance misuse programmes) and further categorised by follow up time - 'shorter-term' (one year), 'medium-term' (one year to two years) and 'long-term' (> two years). RESULTS: Twenty-three of the forty-two studies included in the review reported new onset data. Nine studies reported on differences between surgery types. In those reporting objective measures, all of which were long term, RYGB carried a higher risk than SG, followed by LAGB. All but one study using subjective measures reported a small but significant number of new onset concerning alcohol use, and comparisons between surgery types had more varied results than the objective measures. Studies of substance abuse programmes found high rates of new onset cases (17-60%). CONCLUSION: This systematic review provides support for the consensus guidance suggesting patients should be informed of a small but significant risk of new onset alcohol use following bariatric surgery, with the strongest evidence in the medium- to long-term and in those who have had RYGB followed by SG.

Utilization and Outcomes of Roux-en-Y Gastric Bypass Surgery Following the Affordable Care Act in the United States.

BACKGROUND: The passage of the Affordable Care Act (ACA) in 2010 marked a pivotal moment in American health care policy, significantly expanding access to health care services. This study aims to explore the relationship between the ACA and the utilization and outcomes of Roux-en-Y Gastric Bypass (RYGB) surgery. METHODS: Using data from the National Inpatient Sample (NIS) Database, this retrospective study compares the pre-ACA period (2007-2009) with the post-ACA period (2017-2019), encompassing patients who had RYGB. Multivariable logistic analysis was done accounting for patient's characteristics, comorbidities, and hospital type. RESULTS: In the combined periods, there were 158 186 RYGB procedures performed, with 30.0% transpiring in pre-ACA and 70.0% in the post-ACA. Post-ACA, the proportion of uninsured patients decreased from 4.8% to 3.6% (P < .05), while Black patients increased from 12.5% to 18.5% (P < .05). Medicaid-insured patients increased from 6.8% to 18.1% (P < .05), and patients in the poorest income quartile increased from 20% to 26% (P < .05). Patients in the post-ACA period were less likely to have longer hospital stays (OR = .16: 95% CI .16-.17, P < .01), in-hospital mortality (OR = .29: 95% CI .18-.46, P < .01), surgical site infection (OR = .25: 95% CI .21-.29, P < .01), postop hemorrhage (OR = .24: 95% CI .21-.28, P < .01), and anastomotic leak (OR = .14: 95% CI .10-.18, P < .01) than those in the pre-ACA period. DISCUSSION: Following the implementation of the ACA, utilization of bariatric surgery significantly increased, especially among Black patients, Medicaid beneficiaries, and low-income patients. Moreover, despite the inclusion of more high-risk surgical patients in the post-ACA period, there were better outcomes after surgery.

Impact of RYGB surgery on plasma immunoglobulins: association between blood pressure and glucose levels six months after surgery.

We aimed to study levels of natural antibodies in plasma, and their associations to clinical and fecal biomarkers, before and 6 months after Roux-en-Y gastric bypass (RYGB) surgery. Thirty individuals with obesity [16 type 2 diabetic, 14 non-diabetic (ND)] had RYGB surgery. Total plasma IgA, IgG and IgM antibody levels and specific antibodies to oxidized low-density lipoprotein (oxLDL), malondialdehyde-acetaldehyde adducts, Porphyromonas gingivalis gingipain A hemagglutinin domain (Rgp44), and phosphocholine were measured using chemiluminescence immunoassay. Associations between plasma and fecal antibodies as well as clinical markers were analyzed. RYGB surgery reduced blood pressure, and the glycemic state was improved. A higher level of diastolic blood pressure was associated with lower plasma antibodies to oxLDL after surgery. Also, lower level of glucose markers associated with lower level of plasma antibodies to bacterial virulence factors. Antibodies to oxLDL decreased after surgery, and positive association between active serum lipopolysaccharide and specific oxLDL antibodies was detected. Total IgG levels decreased after surgery, but only in ND individuals. Reduced level of total plasma IgG, improved state of hypertension and hyperglycemia and their associations with decreased levels of specific antibodies in plasma, suggest an improved state of systemic inflammation after RYGB surgery.

Laparoscopic Banded Gastric Bypass: A Case Report of a Successful Weight Loss Despite Gastro-Gastric Fistula.

Obesity is a global health issue, Roux-en-Y gastric bypass (RYGB), is an effective treatment for weight loss. However, some patients experience insufficient weight loss after RYGB, leading to alternative strategies such as adding an adjustable gastric band to the bypass. This case reports a 43-year-old female with morbid obesity who underwent open RYGB in 2004, achieving significant weight loss. However, she experienced weight regain, indicating RYGB failure. A laparoscopic band was placed around her bypass with no post-operative complications and successful steady weight reduction. During follow-up, an upper gastrointestinal series revealed a gastro-gastric fistula. Despite the fistula, the patient maintained a steady weight, with a significant excess weight loss of 40.2% since the banded gastric bypass surgery. The development of a gastro-gastric fistula, which typically affects weight loss outcomes, was managed conservatively without impacting the patient's steady weight maintenance. This highlights an unexpected weight loss outcome in a patient who underwent laparoscopic banding following RYGB failure and later developed a gastro-gastric fistula. Despite the initial RYGB failure, the patient achieved significant weight loss, surpassing the average reported in previous studies.

Internal hernia trends following gastric bypass surgery.

BACKGROUND: Internal hernia is a well-known complication of laparoscopic Roux-en-Y gastric bypass (LRYGB), with reported rates ~ 5% within three months to three years after surgery. Internal hernia through a mesenteric defect can lead to small bowel obstruction. Mesenteric defects began to be more routinely closed, often considered standard practice by 2010. To our knowledge, there are no large population-based studies looking at rates of internal hernia post-LRYGB. This study utilizes a statewide database to characterize the trends of internal hernia post-LRYGB over the last two decades in multiple centers. METHODS: LRYGB procedure records between January 2005 and September 2015 were extracted from the New York SPARCS database. Exclusion criteria included age < 18, in-hospital deaths, bariatric revision procedures, and internal hernia repair during the same hospitalization as LRYGB. Time to internal hernia was calculated from initial LRYGB hospital stay to admission date of the first internal hernia repair record. A multivariable proportional sub-distribution hazards model was utilized to analyze the trend of internal hernia incidence within three-year post-LRYGB. RESULTS: 46,918 patients were identified between 2005 and 2015, with 2950 (6.29) undergoing internal hernia repair post-LRYGB by the end of 2018. The cumulative incidence of internal hernia repair at the 3rd-year post-LRYGB was 4.80% (95% CI: 4.59%-5.02%). By the end of the 13th year, the longest follow-up period, the cumulative incidence was 12.00% (95% CI: 11.30%-12.70%). Overall, there was a decreasing trend over time of undergoing internal hernia repair within three-year post-LRYGB (HR = 0.94, 95% CI: 0.93-0.96), after adjusting for confounding factors. CONCLUSION: This multicenter study maintains the rate of internal hernia following LRYGB reported in smaller studies and provides a longer follow-up period demonstrating decreasing occurrences of internal hernia after bypass as a function of year of index operation. This data is important as internal hernia continues to be a complication post-LRYGB.

The Beauty and the Beast: Bariatric Surgery and a Case of Oxalate Nephropathy.

Oxalate nephropathy is a rare cause of kidney failure. Roux-en-Y gastric bypass surgery is a technique used for surgical treatment of obesity as well as for the treatment of gastric carcinoma. We report the case of a 46-year-old male who was admitted to the nephrology department due to kidney dysfunction eight months after bariatric surgery.

Changes in Fat-Free Mass, Protein Intake and Habitual Physical Activity Following Roux-en-Y Gastric Bypass Surgery: A Prospective Study.

PURPOSE: Large inter-individual variations in post-bariatric fat-free mass loss (FFML) are observed, which might relate to differences in protein intake and physical activity across patients. We performed repetitive assessments of protein intake and physical activity before and after banded Roux-en-Y gastric bypass surgery, and examined its relations to FFML during 6 months of follow-up. MATERIALS AND METHODS: FFML (bio-impedance analyses), protein intake (24-h dietary recalls) and moderate-to-vigorous physical activity (MVPA; activPAL) were assessed in 28 patients (4 males, age 42 ± 12 years) before surgery and at 1-, 3- and 6-months post-surgery. Changes in protein intake and MVPA were evaluated with mixed model analysis, whereas associations with FFML were assessed by univariate regression analysis. RESULTS: Six-month FFML was -7.3 ± 3.6 kg. Protein intake decreased from 80 ± 29 g/day (pre-surgery) to 45 ± 26 g/day (1 month post-surgery (P < 0.001)) and did not improve thereafter (51 ± 21 g/day; P > 0.05). Seven participants (25%) consumed ≥ 60 g protein/day at 6 months post-surgery. Participants performed 7394 ± 2420 steps/day in 54 ± 20 min/day of MVPA, which did not change from pre- to post-surgery (P > 0.05). A higher step count (B = -0.002; 95%CI = [-0.004 - 0.000]; P = 0.048) and higher level of MVPA (B = -0.29; 95%CI = [-0.54 - -0.03]; P = 0.018) were related to a lower FFML. CONCLUSION: A lower post-surgery FFML was attributable to higher MVPA levels but not protein intake. This may be due to the low total protein intake and the observation that only a minority of patients achieved a protein intake ≥ 60 g/day. Future studies should focus on interventions to increase post-bariatric protein intake and MVPA levels.

Post-laparoscopic sleeve gastrectomy, intrathoracic sleeve migration and its management: A case series and review of literature.

De novo or persistent gastro-oesophageal reflux disease which may or may not be associated with injury of the oesophageal mucosa is now a known complication in post-sleeve gastrectomy patients. Repair of hiatal hernias to avoid such circumstances has been commonly performed, although recurrences may occur resulting in migration of gastric sleeve into the thorax, which is now a well-known complication. We report four cases of post-sleeve gastrectomy patients who presented with reflux symptoms, with their contrast-enhanced computed tomography abdomen showing intrathoracic sleeve migration and had hypotensive lower oesophageal sphincter with normal body motility on their oesophageal manometry. A laparoscopic revision Roux-en-Y gastric bypass surgery with hiatal hernia repair was performed for all four of them. No post-operative complications were seen at 1-year follow-up. Laparoscopic reduction of migrated sleeve with posterior cruroplasty and conversion to Roux-en-Y gastric bypass surgery can be safely performed for patients presenting with reflux symptoms in cases of intra-thoracic sleeve migration with good short-term outcomes.

The effect of gastric bypass surgery on cognitive function of Alzheimer's disease and the role of GLP1-SGLT1 pathway.

OBJECTIVE: Gastric bypass surgery has been shown to improve metabolic profiles via GLP1, which may also have cognitive benefits for Alzheimer's disease (AD) patients. However, the exact mechanism requires further investigation. METHODS: Roux-en-Y gastric bypass or sham surgery was performed on APP/PS1/Tau triple transgenic mice (an AD mice model) or wild type C57BL/6 mice. Morris Water Maze (MWM) test was used to evaluate the cognitive function of mice and animal tissue samples were obtained for measurements two months after the surgery. Additionally, STC-1 intestine cells were treated with siTAS1R2 and siSGLT1, and HT22 nerve cells were treated with Aß, siGLP1R, GLP1 and siSGLT1 in vitro to explore the role of GLP1-SGLT1 related signaling pathway in cognitive function. RESULTS: The MWM test showed that bypass surgery significantly improved cognitive function in AD mice as measured by navigation and spatial probe tests. Moreover, bypass surgery reversed neurodegeneration, down-regulated hyperphosphorylation of Tau protein and Aß deposition, improved glucose metabolism, and up-regulated the expression of GLP1, SGLT1, and TAS1R2/3 in the hippocampus. Furthermore, GLP1R silencing down-regulated SGLT1 expression, whereas SGLT1 silencing increased Tau protein deposition and exacerbated dysregulated of glucose metabolism in HT22 cells. However, RYGB did not alter the level of GLP1 secretion in the brainstem (where central GLP1 is mainly produced). Additionally, GLP1 expression was upregulated by RYGB via TAS1R2/3-SGLT1 activation sequentially in the small intestine. CONCLUSION: RYGB surgery could improve cognition function in AD mice through facilitating glucose metabolism and reducing Tau phosphorylation and Aß deposition in the hippocampus, mediated by peripheral serum GLP1 activation of SGLT1 in the brain. Furthermore, RYGB increased GLP1 expression through sequential activation of TAS1R2/TAS1R3 and SGLT1 in the small intestine.

Characteristics and Graft Outcomes of Kidney Transplant Candidates with Enteric Risk Factors and Elevated Plasma Oxalate Levels.

INTRODUCTION: This study describes patient characteristics and examines graft function of kidney transplant recipients (without primary hyperoxaluria) with elevated plasma oxalate (POx) and enteric risk factors prior to transplant at our institution. METHODS: Kidney transplant recipients between 2012 and 2020 with elevated POx at the time of kidney transplant evaluation were included. A matched control cohort was gathered using patient/donor age, living/deceased donor type, panel reactive antibody, kidney donor profile index, and human leukocyte antigen mismatch as matching variables. Graft function at 1 year and at last follow-up was reported. RESULTS: A total of 106 patients with elevated POx were identified. A third of the patients had Roux-en-Y gastric bypass, a third had other enteric risks, and a third did not have an identifiable enteric risk. Median eGFR (estimated glomerular filtration rate) at 1 year and at last follow-up was similar between cases and controls except for subgroup of patients with pre-transplant POx >30 µmol/L where 1-year eGFR was lower compared to controls. Across eGFR categories, more cases were in eGFR category <30 mL/min/1.73 m2 compared to controls. CONCLUSION: Roux-en-Y gastric bypass is the most common identifiable risk for elevated POx in kidney transplant candidates. 1-year graft function was not inferior in cases compared to matched controls except for subgroup with POx >30 µmol/L pre-transplant.

Systematic review on sleeve gastrectomy or Roux-en-Y gastric bypass surgery for refractory gastroparesis.

Management of refractory gastroparesis is challenging after diet, prokinetics, and long-term nutritional support have failed. In this review, the efficacy and safety of surgical interventions (sleeve gastrectomy and Roux-en-Y gastric bypass surgery) are evaluated systematically in patients with refractory gastroparesis. The PubMed, Embase, and Scopus databases were searched to identify relevant studies published up to June 2021. Outcome of interest was symptom improvement and gastric emptying. Nineteen studies with 222 refractory gastroparesis patients (147 Roux-en-Y gastric bypass, 39 sleeve gastrectomy, and 36 subtotal gastrectomy) were included. All studies reported symptom improvement postoperatively, particularly vomiting and nausea. Gastric emptying improved postoperatively in 45% up to 67% for sleeve gastrectomy and 87% for Roux-en-Y gastric bypass. The findings of our systematic review suggest that sleeve gastrectomy and Roux-en-Y gastric bypass surgery improve symptoms and gastric emptying in patients with refractory gastroparesis. Surgery may be effective as treatment for a small group of patients when all other therapies have failed.

The impact of the affordable care act on access to bariatric surgery in Maryland.

INTRODUCTION: This study aims to investigate the influence of the Affordable Care Act (ACA) on the utilization of Roux-en-Y gastric bypass (RYGB) procedures in Maryland. METHODS: Using the Maryland State Inpatient Database, this retrospective study compared all patients undergoing RYGB during the pre-ACA (2007-2009) and post-ACA (2018-2020) periods, including patient demographic factors, pre-existing conditions, and socioeconomic factors. RESULTS: A total of 16,494 RYGB procedures were performed during the study period, of which 12,089 (73.3 â€‹%) were post-ACA. This was a 179.2 â€‹% increase in patients undergoing RYGB post-ACA; nearly triple that of the pre-ACA period. There was a significant decrease in uninsured patients (5.6 â€‹%-1.5 â€‹%, p â€‹< â€‹0.01) an increase in Black patients (32.1 â€‹%-46.8 â€‹%, p â€‹< â€‹0.01) and Medicaid beneficiaries (6.0 â€‹% pre-ACA to 17.8 â€‹% post-ACA, p â€‹< â€‹0.01). There were significant reductions in adverse outcomes (long hospital stays, hemorrhage, GIT leaks, and mortality) across all insurance types (all p â€‹< â€‹0.01). CONCLUSION: The ACA increased access to RYGB procedures, especially in Black and Medicaid recipients in Maryland, enhancing healthcare across all insurance types.

Central Serotonin/Noradrenaline Transporter Availability and Treatment Success in Patients with Obesity.

Serotonin (5-hydroxytryptamine, 5-HT) as well as noradrenaline (NA) are key modulators of various fundamental brain functions including the control of appetite. While manipulations that alter brain serotoninergic signaling clearly affect body weight, studies implicating 5-HT transporters and NA transporters (5-HTT and NAT, respectively) as a main drug treatment target for human obesity have not been conclusive. The aim of this positron emission tomography (PET) study was to investigate how these central transporters are associated with changes of body weight after 6 months of dietary intervention or Roux-en-Y gastric bypass (RYGB) surgery in order to assess whether 5-HTT as well as NAT availability can predict weight loss and consequently treatment success. The study population consisted of two study cohorts using either the 5-HTT-selective radiotracer [11C]DASB to measure 5-HTT availability or the NAT-selective radiotracer [11C]MRB to assess NAT availability. Each group included non-obesity healthy participants, patients with severe obesity (body mass index, BMI, >35 kg/m2) following a conservative dietary program (diet) and patients undergoing RYGB surgery within a 6-month follow-up. Overall, changes in BMI were not associated with changes of both 5-HTT and NAT availability, while 5-HTT availability in the dorsal raphe nucleus (DRN) prior to intervention was associated with substantial BMI reduction after RYGB surgery and inversely related with modest BMI reduction after diet. Taken together, the data of our study indicate that 5-HTT and NAT are involved in the pathomechanism of obesity and have the potential to serve as predictors of treatment outcomes.

Total fecal IgA levels increase and natural IgM antibodies decrease after gastric bypass surgery.

Obesity is associated with low-grade inflammation and increased systemic oxidative stress. Roux-en-Y gastric bypass (RYGB) surgery is known to ameliorate the obesity-induced metabolic dysfunctions. We aimed to study the levels of natural antibodies in feces, before and 6 months after RYGB surgery in obese individuals with and without type 2 diabetes (T2D). Sixteen individuals with T2D and 14 non-diabetic (ND) individuals were operated. Total IgA, IgG and IgM antibody levels and specific antibodies to oxidized low-density lipoprotein (oxLDL), malondialdehyde-acetaldehyde adducts (MAA adducts), Porphyromonas gingivalis gingipain A hemagglutinin domain (Rgp44) and phosphocholine (PCho) were measured using chemiluminescence immunoassay. Total fecal IgA was elevated, while total IgM and IgG were not affected by the surgery. Fecal natural IgM specific to oxLDL decreased significantly in both T2D and ND individuals, while fecal IgM to Rgp44 and PCho decreased significantly in T2D individuals. A decrease in IgG to MAA-LDL, Rgp44 and PCho was detected. RYGB surgery increases the levels of total fecal IgA and decreases fecal natural IgG and IgM antibodies specific to oxLDL. Natural antibodies and IgA are important in maintaining the normal gut homeostasis and first-line defense against microbes, and their production is markedly altered with RYGB surgery.

Effects of Heterozygous Variants in the Leptin-Melanocortin Pathway on Roux-en-Y Gastric Bypass Outcomes: a 15-Year Case-Control Study.

INTRODUCTION: Heterozygous variants in the leptin-melanocortin pathway are associated with obesity. However, their effect on the long-term outcomes after Roux-en-Y gastric bypass (RYGB) is still unknown. METHODS: In this matched case-control study, 701 participants from the Mayo Clinic Biobank with a history of RYGB were genotyped. Sixty-three patients had a heterozygous variant in the leptin-melanocortin pathway. After excluding patients with potential confounders, carriers were randomly matched (on sex, age, body mass index [BMI], and years since surgery) with two non-carrier controls. The electronic medical record of carriers and matched non-carriers was reviewed for up to 15 years after RYGB. RESULTS: A total of 50 carriers and 100 matched non-carriers with a history of RYGB were included in the study. Seven different genes (LEPR, PCSK1, POMC, SH2B1, SRC1, MC4R, and SIM1) in the leptin-melanocortin pathway were identified. At the time of surgery, the mean age was 50.8 ± 10.6 years, BMI 45.6 ± 7.3 kg/m2, and 79% women. There were no differences in postoperative years of follow-up, Roux limb length, or gastric pouch size between groups. Fifteen years after RYGB, the percentage of total body weight loss (%TBWL) in carriers was - 16.6 ± 10.7 compared with - 28.7 ± 12.9 in non-carriers (diff = 12.1%; 95% CI, 4.8 to 19.3) and the percentage of weight regain after maximum weight loss was 52.7 ± 29.7 in carriers compared with 29.8 ± 20.7 in non-carriers (diff = 22.9%; 95% CI, 5.3 to 40.5). The nadir %TBWL was lower - 32.1 ± 8.1 in carriers compared with - 36.8 ± 10.4 in non-carriers (diff = 4.8%; 95% CI 1.8 to 7.8). CONCLUSIONS: Carriers of a heterozygous variant in the leptin-melanocortin pathway have a progressive and significant weight regain in the mid- and long-term after RYGB. Genotyping patients experiencing significant weight regain after RYGB could help implement multidisciplinary and individualized weight loss interventions to improve weight maintenance after surgery.

Evolution of gastroesophageal reflux disease symptoms after bariatric surgery: A dose-response meta-analysis.

BACKGROUND: Obesity is associated with increased prevalence of gastroesophageal reflux disease, with recent reports suggesting improvement in gastroesophageal reflux disease symptoms and weight loss following bariatric surgical intervention. However, the exact impact of the type of bariatric surgery on the evolution of gastroesophageal reflux disease symptoms has remained unexamined. METHODS: We systematically searched electronic databases (PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to December 2018) for eligible studies that satisfy prespecified inclusion criteria. We included clinical trials of all designs that reported on gastroesophageal reflux disease outcomes following laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass. Two independent reviewers extracted relevant data based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Data were pooled using a random-effects model. Main outcomes were symptomatic improvement in gastroesophageal reflux disease symptoms following bariatric surgery. RESULTS: A total of 31 studies were analyzed, and a robust-error meta-regression model was used to conduct a dose-response meta-analysis synthesizing data on 31 studies that reported gastroesophageal reflux disease outcomes after bariatric surgery. Of 5,295 patients who underwent either laparoscopic sleeve gastrectomy (n = 4,715 patients) or laparoscopic Roux-en-Y gastric bypass (n = 580 patients), 63.4% experienced improvement in gastroesophageal reflux disease symptoms (95% CI 32.46-72.18). The dose-response meta-analysis demonstrated a window period of 2 years for sustained improvement after which symptoms began to recur in those that were asymptomatic. CONCLUSION: Bariatric surgery may improve gastroesophageal reflux disease symptoms in obese patients who underwent laparoscopic sleeve gastrectomy; however, the most favorable effect is likely to be found after Roux-en-Y gastric bypass surgery. The effects were not sustained and returned to baseline within 4 years.

Daily transient coating of the intestine leads to weight loss and improved glucose tolerance.

INTRODUCTION: Roux-en-Y gastric bypass surgery (RYGB) has been shown to be the gold standard treatment for obesity associated type-2-diabetes (T2D), however many T2D patients do not qualify or are reluctant to proceed with surgery due to its potential risks and permanent changes to GI anatomy. We have previously described a novel oral formulation, LuCI, that provides a transient coating of the proximal bowel and mimics the effects of RYGB. Herein, we aim to investigate the outcome of chronic LuCI administration on weight and glucose homeostasis. METHODS: Sprague-Dawley rats on a high fat diet achieving diet-induced obesity (DIO) received 5 weeks of daily LuCI or normal saline as control (n = 8/group). Daily weights and glucose tolerance were monitored throughout the experiment. At 5 weeks, systemic blood was sampled through a surgically placed jugular vein catheter, before and during an intestinal glucose bolus, to investigate changes in key hormones involved in glucose metabolism. To elucidate the effects of LuCI on nutrient absorption, fecal output and food intake were measured simultaneously with the analysis of homogenized stool samples performed using bomb calorimetry. RESULTS: At 5 weeks, LuCI animals weighted 8.3% less and had lower fasting glucose levels than Controls (77.6 ±â€¯3.8 mg/dl vs. 99.1 ±â€¯2.7 mg/dl, P < 0.001). LuCI-treated animals had lower baseline insulin and HOMA-IR. Post-prandially, LuCI group had increased GLP-1 and GIP secretion following a glucose challenge. Serum lipid analysis revealed lowered LDL levels highlighting the potential to not only improve glucose control but also modify cardiovascular risk. We then investigated whether LuCI's effect on proximal bowel exclusion may play a role in energy balance. Bomb calorimetry analysis suggested that LuCI reduced calorie absorption with no difference in caloric consumption. CONCLUSION: We demonstrated that LuCI recapitulates the physical and hormonal changes seen after RYGB and can ameliorate weight gain and improve insulin sensitivity in a DIO rat model. Since LuCI's effect is transient and without systemic absorption, LuCI has the potential to be a novel therapy for overweight or obese T2D patients.

Weight loss from caloric restriction vs Roux-en-Y gastric bypass surgery differentially regulates systemic and portal vein GDF15 levels in obese Zucker fatty rats.

Weight loss from caloric restriction (i.e. dieting) tends to be modest and short-lived, whereas from bariatric surgeries such as Roux-en-Y gastric bypass (RYGB) is pronounced and generally sustained. The reasons behind these opposing outcomes between interventions remain unclear, but likely involve differential effects on gut-brain communication. Growth differentiation factor 15 (GDF15) is a ubiquitously-induced, centrally-acting, anorexigenic cytokine whose systemic levels are elevated under a variety of conditions associated with a negative energy balance, including in patients following RYGB. We therefore asked whether systemic and portal vein GDF15 levels differ between obese Zucker fatty rats that experienced similar weight loss from RYGB or from forced caloric restriction (CR). Compared with ad libitum fed (ALF) controls, body weight, visceral adiposity and food intake of RYGB and CR rats were markedly lower during the postoperative observation period. Both systemic and portal vein GDF15 levels in RYGB rats at postoperative day 28 were higher compared with ALF rats and particularly compared with CR rats. Further, systemic and portal vein GDF15 levels negatively correlated with body weight and food intake specifically in RYGB rats. These findings provide evidence that, unlike dieting, RYGB might achieve sustained weight loss and appetite suppression partly through increased GDF15 release from epithelial cells of the gastrointestinal tract.

Leptin Receptors Are Not Required for Roux-en-Y Gastric Bypass Surgery to Normalize Energy and Glucose Homeostasis in Rats.

Sensitization to the adipokine leptin is a promising therapeutic strategy against obesity and its comorbidities and has been proposed to contribute to the lasting metabolic benefits of Roux-en-Y gastric bypass (RYGB) surgery. We formally tested this idea using Zucker fatty fa/fa rats as an established genetic model of obesity, glucose intolerance, and fatty liver due to leptin receptor deficiency. We show that the changes in body weight in these rats following RYGB largely overlaps with that of diet-induced obese Wistar rats with intact leptin receptors. Further, food intake and oral glucose tolerance were normalized in RYGB-treated Zucker fatty fa/fa rats to the levels of lean Zucker fatty fa/+ controls, in association with increased glucagon-like peptide 1 (GLP-1) and insulin release. In contrast, while fatty liver was also normalized in RYGB-treated Zucker fatty fa/fa rats, their circulating levels of the liver enzyme alanine aminotransferase (ALT) remained elevated at the level of obese Zucker fatty fa/fa controls. These findings suggest that the leptin system is not required for the normalization of energy and glucose homeostasis associated with RYGB, but that its potential contribution to the improvements in liver health postoperatively merits further investigation.

A microbial signature following bariatric surgery is robustly consistent across multiple cohorts.

Bariatric surgery induces significant shifts in the gut microbiota which could potentially contribute to weight loss and metabolic benefits. The aim of this study was to characterize a microbial signature following Roux-en-Y Gastric bypass (RYGB) surgery using novel and existing gut microbiota sequence data. We generated 16S rRNA gene and metagenomic sequences from fecal samples from patients undergoing RYGB surgery (n = 61 for 16S rRNA gene and n = 135 for metagenomics) at pre-surgical baseline and one, six, and twelve-month post-surgery. We compared these data with three smaller publicly available 16S rRNA gene and one metagenomic datasets from patients who also underwent RYGB surgery. Linear mixed models and machine learning approaches were used to examine the presence of a common microbial signature across studies. Comparison of our new sequences with previous longitudinal studies revealed strikingly similar profiles in both fecal microbiota composition (r = 0.41 ± 0.10; p < .05) and metabolic pathways (r = 0.70 ± 0.05; p < .001) early after surgery across multiple datasets. Notably, Veillonella, Streptococcus, Gemella, Fusobacterium, Escherichia/Shigella, and Akkermansia increased after surgery, while Blautia decreased. Machine learning approaches revealed that the replicable gut microbiota signature associated with RYGB surgery could be used to discriminate pre- and post-surgical samples. Opportunistic pathogen abundance also increased post-surgery in a consistent manner across cohorts. Our study reveals a robust microbial signature involving many commensal and pathogenic taxa and metabolic pathways early after RYGB surgery across different studies and sites. Characterization of the effects of this robust microbial signature on outcomes of bariatric surgery could provide insights into the development of microbiome-based interventions for predicting or improving outcomes following surgery.