Metabolic Effects Of Bariatric Surgery Research Articles

Cardiac and Metabolic Effects of Bariatric Surgery Among Obese Patients in a Malaysian Tertiary Hospital: A 6-month Prospective Cohort Study.

Obesity is known to be associated with left ventricular diastolic dysfunction due to its effect on blood pressure and glucose tolerance. We aimed to investigate whether weight loss after bariatric surgery might improve diastolic dysfunction through in-depth echocardiographic examination. We recruited twenty-eight patients who were about to undergo bariatric surgery by purposive sampling. They underwent echocardiography at baseline and 6 months after surgery with a focus on diastolic function measurements and global longitudinal strain (GLS). They also had fasting serum lipid and glucose measurements pre- and post-surgery. The mean weight loss after surgery was 24.1 kg. Out of the 28 subjects, fifteen (54%) initially had diastolic dysfunction before surgery. Only two had persistent diastolic dysfunction 6 months after surgery. The mean indexed left atrial volume 6 months post-surgery was 27.1 from 32 ml/m2 prior to surgery. The average E/e' is 11.78 post-surgery from 13.43 pre-surgery. The left ventricular GLS became (-)25.7% after surgery from (-)21.2% prior to surgery. Their post-surgery fasting serum lipid and glucose levels also showed significant improvement. Our study reinforced the existing evidence that bariatric surgery significantly improved echocardiographic parameters of diastolic function and left ventricular global longitudinal strain, along with various metabolic profiles.

Effect of Bariatric Surgery on Plasma Cell-Free Mitochondrial DNA, Insulin Sensitivity and Metabolic Changes in Obese Patients.

While improvement of mitochondrial function after bariatric surgery has been demonstrated, there is limited evidence about the effects of bariatric surgery on circulatory cell-free (cf) mitochondrial DNA (mtDNA) and intracellular mtDNA abundance. Plasma and peripheral blood mononuclear (PBM) cells were isolated from healthy controls (HC) and bariatric surgery patients before surgery and 2 weeks, 3 months, and 6 months after surgery. At baseline, the plasma level of short cf-mtDNA (ND6, ~100 bp) fragments was significantly higher in obese patients compared to HC. But there was no significant variation in mean ND6 values post-surgery. A significant positive correlation was observed between preop plasma ND6 levels and HgbA1c, ND6 and HOMA-IR 2 weeks post-surgery, and mtDNA content 6 months post-surgery. Interestingly, plasma from both HC and obese groups at all time points post-surgery contains long (~8 kb) cf-mtDNA fragments, suggesting the presence of near-intact and/or whole mitochondrial genomes. No significant variation was observed in mtDNA content post-surgery compared to baseline data in both PBM and skeletal muscle samples. Overall, bariatric surgery improved insulin sensitivity and other metabolic parameters without significant changes in plasma short cf-mtDNA levels or cellular mtDNA content. Our study provides novel insights about possible molecular mechanisms underlying the metabolic effects of bariatric surgery and suggests the development of new generalized approaches to characterize cf-mtDNA.

282-LB: Analysis of Cell-Free Mitochondrial DNA in Obese Patients With and Without Type 2 Diabetes after Bariatric Surgery

While the improvement of mitochondrial function after bariatric surgery was shown, there is limited evidence about the metabolic effects of bariatric surgery on circulatory cell-free (cf) mitochondrial DNA (mtDNA). Therefore, the goal of this study was to compare plasma levels of cf-mtDNA in the association to the metabolic changes before and after surgery in obese patients. Plasma was isolated from 13 morbidly obese bariatric surgery patients with and without type 2 diabetes (T2D) and 8 healthy controls (HC). From each obese patient, blood was collected at baseline, 2 weeks, 3 and 6 months after surgery. QRT-PCR was used to quantify short cf-mtDNA (~100 bp) in isolated plasma within the ND6 region. At baseline, plasma level of short cf-mtDNA fragments was significantly higher in obese patients compared to HC. Additionally, when obese patients were grouped by presence or absence of T2D and compared to HC patients, plasma ND6 levels were significantly higher in obese T2D but not in non-T2D group. Bariatric surgery reduced BMI and improved insulin sensitivity and other whole-body metabolic parameters in all obese patients. No significant variation in mean ND6 values over time was observed post-surgery in all obese patients or when we plotted the data according to the T2D and non-T2D. Importantly, significant positive correlation was observed between plasma ND6 level and HOMA-IR but only 2 weeks post-surgery. Interestingly, plasma from both HC and obese groups at all time points post-surgery contain long (~8 kb) cf-mtDNA fragments, suggesting the presence of near intact and/or whole mitochondrial genomes. Overall, bariatric surgery decreased weight and improved insulin sensitivity and other metabolic parameters in obese patients without significant change in plasma cf-mtDNA levels. Further studies need to test potential determinants, characteristics and origin of cf-mtDNA associated with postoperative metabolic improvements following surgery. Disclosure L. Yuzefovych: None. V. M. Pastukh: None. W. Richards: Research Support; Ethicon, Inc. L. Rachek: None. Funding University of South Alabama (807 to L.R., W.R.)

FAM3D: A gut secreted protein and its potential in the regulation of glucose metabolism

The number of diabetic patients is rising globally and concomitantly so do the diabetes associated complications. The gut secretes a variety of proteins to control blood glucose levels and/or food intake. As the drug class of GLP-1 agonists is based on a gut secreted peptide and the positive metabolic effects of bariatric surgery are at least partially mediated by gut peptides, we were interested in other gut secreted proteins which have yet to be explored. In this respect we identified the gut secreted protein FAM3D by analyzing sequencing data from L- and epithelial cells of VSG and sham operated as well as chow and HFD fed mice. FAM3D was overexpressed in diet induced obese mice via an adeno-associated virus (AAV), which resulted in a significant improvement of fasting blood glucose levels, glucose tolerance and insulin sensitivity. The liver lipid deposition was reduced, and the steatosis morphology was improved. Hyperinsulinemic clamps indicated that FAM3D is a global insulin sensitizer and increases glucose uptake into various tissues. In conclusion, the current study demonstrated that FAM3D controls blood glucose levels by acting as an insulin sensitizing protein and improves hepatic lipid deposition.

A multi-marker integrative analysis reveals benefits and risks of bariatric surgery

Bariatric surgery (BS) is an effective intervention for severe obesity and associated comorbidities. Although several studies have addressed the clinical and metabolic effects of BS, an integrative analysis of the complex body response to surgery is still lacking. We conducted a longitudinal data study with 36 patients with severe obesity who were tested before, 6 and 12 months after restrictive BS for more than one hundred blood biomarkers, including clinical, oxidative stress and metabolic markers, peptide mediators and red blood cell membrane lipids. By using a synthetic data-driven modeling based on principal component and correlation analyses, we provided evidence that, besides the early, well-known glucose metabolism- and weight loss-associated beneficial effects of BS, a tardive, weight-independent increase of the hepatic cholesterol metabolism occurs that is associated with potentially detrimental inflammatory and metabolic effects. Canonical correlation analysis indicated that oxidative stress is the most predictive feature of the BS-induced changes of both glucose and lipids metabolism. Our results show the power of multi-level correlation analysis to uncover the network of biological pathways affected by BS. This approach highlighted potential health risks of restrictive BS that are disregarded with the current practice to use weight loss as surrogate of BS success.

Long-term improvement of adipocyte insulin action during body weight relapse after bariatric surgery: a longitudinal cohort study.

There are few long-term mechanistic studies in adipose tissue that investigate the metabolic effects of bariatric surgery. Changes in lipogenesis may be involved in long-term weight development. To investigate the long-term effect of bariatric surgery on lipogenesis in abdominal fat cells and whether surgical treatment could induce an epigenetic memory that would maintain improved lipogenesis in spite of body weight relapse. Karolinska University Hospital in Stockholm County, Sweden. A total of 22 women with obesity living in the Stockholm area were examined before, 2, 5, and 10 years after bariatric surgery. Abdominal adipose tissue biopsies were obtained. Fat cells were isolated and spontaneous and insulin stimulated glucose incorporation into lipids were assayed. CpG-methylation profiling was performed on adipocytes using the Infinium EPIC BeadChips. Bariatric surgery was associated with improvement in adipocyte spontaneous and insulin stimulated lipogenesis, which was maintained despite some later weight regain (29 % of initial weight loss). There was also an increase in fat cell size between 2- and 10-year follow-up, albeit not to presurgery levels. There were 7729 differentially methylated CpG sites (DMS) at 2 years that showed no sign of return to baseline at either 5 or 10 years. Merging results with expression profiles identified 1259 genes with DMS which showed early response or continual change in expression in one direction after surgery. Upregulated genes with DMS were enriched in gene sets linked to cellular response to insulin stimulus (e.g., IRS1, IRS2, PDE3B, and AKT2) and regulation of lipid metabolic processes. Bariatric surgery leads to long-term improvement of lipogenesis and insulin responsiveness in subcutaneous adipocytes in women in spite of some partial body weight regain postoperatively. This may to some extent be explained by epigenetic modifications of fat cell function.

Are the Changes in Gastrointestinal Hormone Secretion Necessary for the Success of Bariatric Surgery? A Critical Review of the Literature.

Ghrelin, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) are involved in energy balance regulation and glucose homeostasis. Obesity is characterized by lower fasting levels and blunted postprandial responses of ghrelin, GLP-1, and possibly PYY. Both Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) have been shown to increase postprandial GLP-1 and PYY levels. Human studies have shown that enhanced postprandial GLP-1 and PYY release are associated with favorable weight loss outcomes after RYGB. However, studies in knockout mice have shown that GI hormones are not required for the primary metabolic effects of bariatric surgery. Here, we summarize the complex interaction between obesity, bariatric surgery, and GI hormones in order to determine the exact role of GI hormones in the success of bariatric surgery.

Bariatric Surgery in Patients with Super-Super Obesity Causes Metabolic Improvement Beyond Weight Loss

Background: Extreme obesity leads to increased health risks and perioperative complications. The results of bariatric surgery in patients with super-super obesity (SSO) are presented in this study. Methods: From April 2008 to August 2019, 60 patients with super-super obesity underwent bariatric surgery. Their weight loss and outcome were analyzed. The mean follow-up time was 72.25 months. Results: At baseline, the mean age was 41.5 years old, the mean BMI was 63.81 kg/m2, 80% of the patients suffered from co-morbidities, and 23.33% were revisional surgeries. Weight loss continued for up to two years after surgery. The percentage of excess weight lost at two years was 62.27%, from two to five years: 61.48%, from five to 10 years: 36.82% and after ten years it was 31.89% (P<.001). The mean at last follow-up BMI was 45.11 kg/m2 and 48.33% of the patients failed to lose at least 50% of excess weight. Patients with fatty liver, diabetes, sleep apnea and hyperlipidemia had a cure or improvement in more than 70% of the cases. There were 5% complications and two (3.33%) deaths were reported. Conclusion: Bariatric surgery in patients with SSO was feasible and safe. The amount of weight loss achieved was acceptable in the short term but decreased in the long term, almost 50% of the patients failed to decrease excess overweight of 50%. The metabolic effects of bariatric surgery were maintained during the follow-up time despite the increase in weight. However, the third or more revisional bariatric surgery increased the risk of mortality. Trial Registration: Clinicaltrials.gov (number NCT04663425). Funding Statement: There were no sources of support for the work being reported. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The study was approved by the Assuta Helsinki review board (number 2015-073).

Comparación de parámetros metabólicos en pacientes adultos y ancianos sometidos a cirugía bariátrica: Una cohorte prospectiva

Introducción: El Objetivo fue evaluar los parámetros metabólicos en pacientes adultos ≥ 65 años en comparación con adultos &lt; 65 años sometidos a CB pre y post intervención.Materiales y métodos: Estudio analítico de cohorte prospectiva en 40 pacientes sometidos a CB durante el periodo julio de 2015 y marzo de 2018. Los pacientes fueron divididos en dos grupos (A: ≥65 años; B: &lt; 65 años) y se evaluaron previo a la cirugía (basal), y a los 3 y 6 meses posteriores al acto quirúrgico parámetros antropométricos y parámetros bioquímicos. Se calculó el porcentaje de peso perdido (PEPP) y se evaluó el índice Triglicéridos/HDLc (TAG/HDLc) como marcador de insulinorresistencia.Resultados: De los 40 pacientes sometidos a la CB, se incluyeron 36: 21 pacientes eran del grupo A (mediana de edad: 59, RIQ: 48-61 años) y 15 pacientes del grupo B (mediana de edad: 67, RIQ: 66-69 años), el porcentaje de pacientes con diabetes mellitus tipo 2 era de 53%(n=8) en B vs 43% (n=9) en A. Luego de 3 y 6 meses post CB se observó en el grupo B un descenso en el peso, índice de masa corporal y porcentaje de exceso de peso perdido (PEPP) no significativo, disminución en los niveles de glucemia y HbA1c sumado a un aumento significativo en los niveles de HDLc, además de un descenso significativo del índice TAG/HDLc en el grupo B. Se encontró una correlación positiva entre los niveles de HbA1c y PEPP, HDLc y el índice TAG/HDLc así como el descenso del uso de antidiabéticos e hipolipemiantes en el grupo B. Conclusiones: la CB logró similares resultados antropométricos en el grupo de pacientes ≥ de 65 años presentando una mejoría significativa en los paramétricos metabólicos a los 3 y 6 meses, principalmente en la insulinorresistencia, lo cual apoyaría el beneficio de la CB en este grupo etario.

Significance of intestinal microbiota in implementing metabolic effects of bariatric surgery

Bariatric surgery is among successful methods of obesity treatment, with effects going beyond weight reduction alone, but rather involving improved glucose tolerance, along with control or remission of the type 2 diabetes mellitus. The precise mechanisms causing metabolic effects of bariatric surgery are not fully elucidated, even though substantial evidence suggest that they include changes in the gut microbiota, bile acid homeostasis, and the close interactions of these factors. Intestinal microflora is directly involved in the energy metabolism of a host human. Obesity and type 2 diabetes mellitus are associated with certain changes in the species composition and diversity of intestinal microflora, which are considered important factors in the development and progression of these ailments. Bariatric surgery leads to significant and persistent changes in the composition of the intestinal microbiota, often bringing it closer to the characteristics of the microbiota of an average person with a normal weight. An important role in implementing the metabolic effects of bariatric surgery, primarily in the improvement of glucose metabolism, belongs to postoperative changes in homeostasis of bile acids. These changes imply close metabolism. Moreover, changes in the bile acid metabolism after bariatric surgery affect the microbiota of the host. Further study of these relationships would clarify the mechanisms underlying metabolic surgery, make it more predictable, targeted and controlled, as well as open new therapeutic targets in the treatment of obesity and associated conditions.

Metabolic effects of bariatric surgery on patients with type 2 diabetes: a population-based study.

Bariatric surgery among patients with obesity and type 2 diabetes (T2D) can induce complete remission. However, it remains unclear whether sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) has better T2D remission within a population-based daily practice. To compare patients undergoing RYGB and SG on the extent of T2D remission at the 1-year follow-up. Nationwide, population-based study including all 18 hospitals in the Netherlands providing metabolic and bariatric surgery. Patients undergoing RYGB and SG between October 2015 and October 2018 with 1 year of complete follow-up data were selected from the mandatory nationwide Dutch Audit for Treatment of Obesity (DATO). The primary outcome is T2D remission within 1 year. Secondary outcomes include ≥20% total weight loss (TWL), obesity-related co-morbidity reduction, and postoperative complications with a Clavien-Dindo (CD) grade ≥III within 30 days. We compared T2D remission between RYGB and SG groups using propensity score matching to adjust for confounding by indication. A total of 5015 patients were identified from the DATO, and 4132 (82.4%) had completed a 1-year follow-up visit. There were 3350 (66.8%) patients with a valid T2D status who were included in the analysis (RYGB = 2623; SG = 727). RYGB patients had a lower body mass index than SG patients, but were more often female, with higher gastroesophageal reflux disease and dyslipidemia rates. After adjusting for these confounders, RYGB patients had increased odds of achieving T2D remission (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.14-2.1; P < .01). Groups were balanced after matching 695 patients in each group. After matching, RYGB patients still had better odds of T2D remission (OR, 1.91; 95% CI, 1.27-2.88; P < .01). Also, significantly more RYGB patients had ≥20%TWL (OR, 2.71; 95% CI, 1.96-3.75; P < .01) and RYGB patients had higher dyslipidemia remission rates (OR, 1.96; 95% CI, 1.39-2.76; P < .01). There were no significant differences in CD ≥III complications. Using population-based data from the Netherlands, this study shows that RYGB leads to better T2D remission rates at the 1-year follow-up and better metabolic outcomes for patients with obesity and T2D undergoing bariatric surgery in daily practice.

Additional Metabolic Effects of Bariatric Surgery in Patients with a Poor Mid-Term Weight Loss Response: A 5-Year Follow-Up Study.

To ascertain the 5-year metabolic effects of bariatric surgery in poor weight loss (WL) responders and establish associated factors. Methods: Retrospective analysis of a non-randomised prospective cohort of bariatric surgery patients completing a 5-year follow-up. Mid-term poor WL was considered when 5-year excess weight loss was <50%. Results: Forty-three (20.3%) of the 212 included patients were mid-term poor WL responders. They showed an improvement in all metabolic markers at 2 years, except for total cholesterol. This improvement with respect to baseline was maintained at 5 years for plasma glucose, HbA1c, HOMA, HDL and diastolic blood pressure; however, LDL cholesterol, triglycerides and systolic blood pressure were similar to presurgical values. Comorbidity remission rates were comparable to those obtained in the good WL group except for hypercholesterolaemia (45.8% vs. poor WL, p = 0.005). On multivariate analysis, lower baseline HDL cholesterol levels, advanced age and lower preoperative weight loss were independently associated with poor mid-term WL. Conclusions: Although that 1 in 5 patients presented suboptimal WL 5 years after bariatric surgery, other important metabolic benefits were maintained.

Endocannabinoid Receptor-1 and Sympathetic Nervous System Mediate the Beneficial Metabolic Effects of Gastric Bypass

SUMMARYThe exact mechanisms underlying the metabolic effects of bariatric surgery remain unclear. Here, we demonstrate, using a combination of direct and indirect calorimetry, an increase in total resting metabolic rate (RMR) and specifically anaerobic RMR after Roux-en-Y gastric bypass (RYGB), but not sleeve gastrectomy (SG). We also show an RYGB-specific increase in splanchnic sympathetic nerve activity and “browning” of visceral mesenteric fat. Consequently, selective splanchnic denervation abolishes all beneficial metabolic outcomes of gastric bypass that involve changes in the endocannabinoid signaling within the small intestine. Furthermore, we demonstrate that administration of rimonabant, an endocannabinoid receptor-1 (CB1) inverse agonist, to obese mice mimics RYGB-specific effects on energy balance and splanchnic nerve activity. On the other hand, arachidonoylethanolamide (AEA), a CB1 agonist, attenuates the weight loss and metabolic signature of this procedure. These findings identify CB1 as a key player in energy regulation post-RYGB via a pathway involving the sympathetic nervous system.

Mechanism of Bile Acid Reabsorption in the Biliopancreatic Limb After Duodenal-Jejunal Bypass in Rats.

Bile acids (BAs) are important in the metabolic effects of bariatric surgery. Most BAs are reabsorbed in the ileum and recycled back to the liver. We have reported that this enterohepatic circulation was shortened by duodenal-jejunal bypass (DJB), and the biliopancreatic (BP)-limb plays an important role in reabsorption of BAs. However, the mechanism of BA reabsorption in BP-limb remains uncertain. We aimed to investigate the mechanisms of BA reabsorption after DJB, especially focusing on carrier-mediated transport of BAs and the impact of the presence or absence of lipids on BA reabsorption. Otsuka-Long-Evans-Tokushima fatty rats or Sprague-Dawley rats were assigned to a control group and DJB group. BA levels in the divided small intestine were quantified with liquid chromatography-mass spectrometry. Labeled BA was injected and perfused with BA transporter inhibitors or mixture of lipids in the isolated BP-limb, and bile was sampled and analyzed. Conjugated BA levels in the BP-limb were significantly higher than that of the control group. BA absorption tended to decrease by the apical sodium-dependent BA transporter inhibitor and was significantly decreased by the organic anion-transporting peptide (OATP) inhibitor. BA absorption tended to increase in the absence of lipid solutions compared with that in the presence of lipid solutions. We attributed the increased BA reabsorption in the BP-limb to lack of food in the BP-limb, which contains concentrated BAs and no lipids. OATP played an important role in BA reabsorption in the BP-limb. Therefore, BAs would be reabsorbed in different manners after DJB.

Insulin resistance in bariatric surgery.

To give an updated review on the underlying mechanisms and clinical effects of improved glucose control after bariatric surgery. The basic principles of the mechanism for the metabolic effects of bariatric surgery can be categorized into calorie restriction, deviation of nutrients, and reduced amounts of adipose tissue. Recent findings suggest the importance of early changes following deviation of nutrients to more distal parts of the small bowel resulting in altered release of gastrointestinal hormones, altered gut microbiota, and weight-reduction. In the long-term, loss of adipose tissue results in reduced inflammation and improved insulin sensitivity. From a clinical perspective these changes are associated with remission of diabetes in patients with morbid obesity and type 2 diabetes, prevention of diabetes in patients with insulin resistance without overt type 2 diabetes and prevention of both microvascular and macrovascular complications for all patients with morbid obesity. At present, bariatric surgery remains the most effective treatment option to improve glucose control and long-term complications associated with hyperglycemia in patients with obesity.Although the mechanisms behind these metabolic effects remain only partially understood, further knowledge on these complex mechanisms may help identifying durable treatment options for morbid obesity and important metabolic comorbidities.

Multiagonist Unimolecular Peptides for Obesity and Type 2 Diabetes: Current Advances and Future Directions.

The ever-increasing prevalence of obesity and Type 2 diabetes has necessitated the development of newer and more effective approaches for achieving efficient glycemic control and weight loss. Conventional treatment methods often result in weight gain, further deteriorating the already impaired metabolic control in people with obesity/Type 2 diabetes. Alleviation of obesity and diabetes achieved after bariatric surgeries highlight the therapeutic importance of gut-brain axis and entails development of more patient-friendly approaches replicating the positive metabolic effects of bariatric surgery. Given the potential involvement of several gut hormones in the success of bariatric surgery, the therapeutic importance of synergistic interaction between these hormones for improved metabolism cannot be ignored. Many unimolecular multiagonist peptides are in preclinical and clinical trials as they maximize the combinatorial metabolic efficacy by concurrent activation of multiple gut hormone receptors. This review summarizes the ongoing developments of multiagonist peptides as novel therapeutic approaches against obesity-diabetes.

Gastric mucosal devitalization (GMD): translation to a novel endoscopic metabolic therapy.

Background and study aims The metabolic effects of bariatric surgery may partially result from removal of the gastric mucosa, an often underappreciated endocrine organ. Using argon plasma coagulation (APC), we may be able to selectively devitalize (ablate) the mucosa. The aim of this study was to identify the optimal tissue color that would correspond to selective gastric mucosal devitalization (GMD) using ex-vivo human stomach specimens. Patients and methods Stomach specimens were obtained at sleeve gastrectomy. Prior to APC application, a submucosal fluid cushion was created. APC was then applied over a 2 × 2-cm area to the fundus and body, aiming for the three indicator colors (white, golden, brown). Pathological analysis was then performed independently and in a blinded fashion by two pathologists to determine the depth of mucosal and submucosal percent thermal injury and mucosal percent cell death. Results Six patients were enrolled. There was a significant correlation between tissue color and mucosal percent thermal injury. The highest percent mucosal thermal injury was seen with brown (99.6 %, 95 % CI: 98.7, 100), followed by golden (92.5 %, 95 % CI: 85.5, 99.5), and then white (75.2 %, 95 % CI: 58.3, 92.1, P < 0.01). Submucosal thermal injury was seen in 88.9 % of the slides. Greater than minimal submucosal injury (> 10 % depth) was found significantly more with brown tissue color (91.6 %) than golden (75 %) or white (33.3 %, P < 0.05). However, 91.7 % of the entire sample set < 50 % injury. Conclusion GMD is achievable using APC without thermal injury to muscularis propria. A golden color results in sufficient mucosal injury with only superficial injury to the submucosa.

Global transcriptome analysis of rat hypothalamic arcuate nucleus demonstrates reversal of hypothalamic gliosis following surgically and diet induced weight loss

The central mechanisms underlying the marked beneficial metabolic effects of bariatric surgery are unclear. Here, we characterized global gene expression in the hypothalamic arcuate nucleus (Arc) in diet-induced obese (DIO) rats following Roux-en-Y gastric bypass (RYGB). 60 days post-RYGB, the Arc was isolated by laser-capture microdissection and global gene expression was assessed by RNA sequencing. RYGB lowered body weight and adiposity as compared to sham-operated DIO rats. Discrete transcriptome changes were observed in the Arc following RYGB, including differential expression of genes associated with inflammation and neuropeptide signaling. RYGB reduced gene expression of glial cell markers, including Gfap, Aif1 and Timp1, confirmed by a lower number of GFAP immunopositive astrocyte profiles in the Arc. Sham-operated weight-matched rats demonstrated a similar glial gene expression signature, suggesting that RYGB and dietary restriction have common effects on hypothalamic gliosis. Considering that RYGB surgery also led to increased orexigenic and decreased anorexigenic gene expression, this may signify increased hunger-associated signaling at the level of the Arc. Hence, induction of counterregulatory molecular mechanisms downstream from the Arc may play an important role in RYGB-induced weight loss.

Longitudinal changes of microbiome composition and microbial metabolomics after surgical weight loss in individuals with obesity

BackgroundSome of the metabolic effects of bariatric surgery may be mediated by the gut microbiome. ObjectivesTo study the effect of bariatric surgery on changes to gut microbiota composition and bacterial pathways, and their relation to metabolic parameters after bariatric surgery. SettingsUniversity hospitals in the United States and Spain. MethodsMicrobial diversity and composition by 16 S rRNA sequencing, putative bacterial pathways, and targeted circulating metabolites were studied in 26 individuals with severe obesity, with and without type 2 diabetes, before and at 3, 6, and 12 months after either gastric bypass or sleeve gastrectomy. ResultsBariatric surgery tended to increase alpha diversity, and significantly altered beta diversity, microbiota composition, and function up to 6 months after surgery, but these changes tend to regress to presurgery levels by 12 months. Twelve of 15 bacterial pathways enriched after surgery also regressed to presurgery levels at 12 months. Network analysis identified groups of bacteria significantly correlated with levels of circulating metabolites over time. There were no differences between study sites, surgery type, or diabetes status in terms of microbial diversity and composition at baseline and after surgery. ConclusionsThe association among changes in microbiome with decreased circulating biomarkers of inflammation, increased bile acids, and products of choline metabolism and other bacterial pathways suggest that the microbiome partially mediates improvement of metabolism during the first year after bariatric surgery.

2113-P: Metabolic Effects of Bariatric Surgery in a Group of Patients Aged 65 Years Old or More Compared with a Group of Adults Younger Than 65 Years Old—A Prospective Cohort

Aim: We compared the anthropometric and metabolic parameters before and after six months of bariatric surgery (BS) between a group of patients aged ≥65 and &amp;lt;65 years old (y/o) with or without comorbidities. Materials and Methods: We did a prospective study with patients who had undergone BS and followed them for six months from July, 2015 to May, 2018 at Milstein hospital, Argentina and divided them into two cohorts: older and younger than 65 y/o. Outcomes were compared (lost weight [LW], excess weight loss percentage [EWLP], BMI, A1c hemoglobin [HbA1c], HDL, Triglycerides [Tg] and Tg/HDL ratio) and we considered a p &amp;lt;0.05 as statistically significant. Results: We included 36 patients, 15 were ≥65 y/o and 21 &amp;lt;65 y/o. There were more patients with type 2 diabetes mellitus (DM2) in the oldest group. We found no statistical difference between groups in WL and the EWLP but observed a statistical rise in the levels of HDL (43, RIQ 95% CI: 39-48 vs. 51, RIQ 95% CI: 44-55, p=0.026) and the decrease of the Tg/HDL ratio (1.6 RIQ 95% CI: 1.4-2.1 vs. 3.1 RIQ 95% CI: 2.2-4.6, p=0.02) in the group of ≥65 y/o. The HbA1c levels were significantly higher in the &amp;gt; 65 y/o with DM2 and the decrease was statistically greater after the follow-up. When we compared initial treatment for DM2 after 3 and 6 months of BS, there was a statistically significant decrease in the use of oral antidiabetic drugs and insulin (chi2= 19%, p=0.004 at 3 months, chi2: 27%, p&amp;lt;0.001 at 6 months after surgery). If we analyzed this result by age, there was no difference between both cohorts (chi2=3.73, p=0.15 and chi2=1.46, p=0.4 at 3 and 6 months after surgery respectively). Conclusion: We found a significant benefit in metabolic effects of BS in the ≥65 y/o cohort, especially by decreasing insulin resistance, even in those patients without diagnosis of DM2. We need more studies and a greater sample size to generalize these results. Disclosure C. Musso: None. F.A. Di Fermo Gomez: None. J. Rosenfarb: None. L. Bosio: None. J. Santamaria: None. M. Hansen: None. C. Gimenez: None. A.G. Errasti: None. D. Caruso: Other Relationship; Self; Novartis Pharmaceuticals Corporation. M.C. Faingold: None.