Beneficial Effects Of Bariatric Surgery Research Articles

Influence of Bariatric Surgery on Gut Microbiota Composition and Its Implication on Brain and Peripheral Targets.

Obesity remains a significant global health challenge, with bariatric surgery remaining as one of the most effective treatments for severe obesity and its related comorbidities. This review highlights the multifaceted impact of bariatric surgery beyond mere physical restriction or nutrient malabsorption, underscoring the importance of the gut microbiome and neurohormonal signals in mediating the profound effects on weight loss and behavior modification. The various bariatric surgery procedures, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), act through distinct mechanisms to alter the gut microbiome, subsequently impacting metabolic health, energy balance, and food reward behaviors. Emerging evidence has shown that bariatric surgery induces profound changes in the composition of the gut microbiome, notably altering the Firmicutes/Bacteroidetes ratio and enhancing populations of beneficial bacteria such as Akkermansia. These microbiota shifts have far-reaching effects beyond gut health, influencing dopamine-mediated reward pathways in the brain and modulating the secretion and action of key gut hormones including ghrelin, leptin, GLP-1, PYY, and CCK. The resultant changes in dopamine signaling and hormone levels contribute to reduced hedonic eating, enhanced satiety, and improved metabolic outcomes. Further, post-bariatric surgical effects on satiation targets are in part mediated by metabolic byproducts of gut microbiota like short-chain fatty acids (SCFAs) and bile acids, which play a pivotal role in modulating metabolism and energy expenditure and reducing obesity-associated inflammation, as well as influencing food reward pathways, potentially contributing to the regulation of body weight and reduction in hedonic eating behaviors. Overall, a better understanding of these mechanisms opens the door to developing non-surgical interventions that replicate the beneficial effects of bariatric surgery on the gut microbiome, dopamine signaling, and gut hormone regulation, offering new avenues for obesity treatment.

The Effect of Non-Alcoholic Fatty Liver Disease on Weight Loss and Resolution of Obesity-Related Disorders After Bariatric Surgery

BackgroundPatients undergoing bariatric surgery have a high incidence of non-alcoholic fatty liver disease (NAFLD). However, the effect of NAFLD or non-alcoholic steatohepatitis (NASH) on the weight loss and resolution of obesity-related disorders is a matter of debate.MethodsIn this study, we compare the long-term outcomes after bariatric with the presence of NAFLD in the liver biopsy at the time of surgery.ResultsThe follow-up was available for 226 out of 288 patients. The mean follow-up time was 24.9 (± 13.6) months. The baseline histology showed that 112 patients (38.9%) had no NASH, 70 (24.3%) were borderline, and 106 (36.8%) had NASH. At follow-up, the mean BMI dropped from (52 ± 10.2) to (36.6 ± 8) kg/m 2. Excess weight loss (EWL) was similar in all NAFLD groups. Type 2 diabetes mellitus dropped from 35.7 to 11.4%, hypertension from 65.6 to 36.7%, hyperlipidemia from 62.3 to 33%, and obstructive sleep apnea from 37.5 to 14.9%. Only hyperlipidemia was significantly associated with NASH compared to the groups with no NASH or borderline NASH (p value = 0.002 and p value = 0.04, respectively) during the first two years of follow-up.ConclusionThe beneficial effects of bariatric surgery are evident across all patients with NAFLD. Patients with NASH have comparable outcomes regarding weight loss and resolution of obesity-related comorbidities.

Bariatric surgery and its impact on depressive symptoms, cognition, brain and inflammation.

Obesity has been associated with depressive symptoms and impaired cognition, but the mechanisms underlying these relationships are not well understood. It is also not clear whether reducing adiposity reverses these behavioral outcomes. The current study tested the impact of bariatric surgery on depressive symptoms, cognition, and the brain; using a mediation model, we also examined whether the relationship between changes in adiposity after the surgery and those in regional thickness of the cerebral cortex are mediated by changes in low-grade inflammation (as indexed by C-reactive protein; CRP). A total of 18 bariatric patients completed 3 visits, including one baseline before the surgery and two post-surgery measurements acquired at 6- and 12-months post-surgery. Each visit consisted of a collection of fasting blood sample, magnetic resonance imaging of the brain and abdomen, and assessment of depressive symptoms and cognition. After surgery, we observed reductions of both visceral fat (p< 0.001) and subcutaneous fat (p< 0.001), less depressive symptoms (p< 0.001), improved verbal reasoning (p< 0.001), and reduced CRP (p< 0.001). Mediation analyses revealed that the relationships between the surgery-related changes in visceral fat and cortical thickness in depression-related regions are mediated by changes in CRP (ab=-.027, SE=.012, 95% CI [-.054, -,006]). These findings suggest that some of the beneficial effects of bariatric surgery on brain function and structure are due to a reduction of adiposity-related low-grade systemic inflammation.

Increased Glucagon Immunoreactivity in a Rat Model of Diet-Induced Obesity following Sleeve Gastrectomy

Objective: Bariatric surgery is currently the most effective treatment for obesity, and procedures such as Roux-en-Y gastric bypass and sleeve gastrectomy (SG) also result in rapid improvements in insulin sensitivity and glucose tolerance. In addition, these procedures cause changes in the secretion of various gut-derived hormones. The role these hormones play in the mechanism of the beneficial effects of bariatric surgery is still debated, but nonetheless, their importance provides inspiration for novel obesity-targeted pharmacotherapies. Methods: Male Sprague-Dawley rats were fed either regular chow or a cafeteria diet to induce obesity. A sub-group of the obese animals then underwent either sham surgery or SG. Results: Following a 4-week recovery period, SG rats weighed significantly less than obese or sham-operated rats. Improvements in glucose tolerance and insulin sensitivity also occurred in the SG group, but these were not always statistically significant. We measured the intracellular lipid content of liver samples and found that obese rats showed signs of non-alcoholic fatty liver disease, which were significantly ameliorated by SG. There were significantly higher glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide responses to a standard mixed meal in the SG group, as well as paradoxically higher glucagon secretion. Conclusion: These data highlight the need for more specific anti-glucagon antibodies to characterize the changes in proglucagon-derived peptide concentrations that occur following SG. Further studies are required to determine whether these peptides contribute to the therapeutic effects of SG.

Bariatric Surgery and Myocardial Mechanics: A Meta-Analysis of Speckle Tracking Echocardiographic Studies.

Aim: Current evidence on the effects of bariatric surgery on cardiac mechanics in patients with obesity is based on a few single studies. We investigated this issue through a meta-analysis of speckle tracking echocardiography (STE) studies that reported data on changes in left ventricular (LV) mechanics as assessed by global longitudinal strain (GLS). Methods: The PubMed, OVID-MEDLINE and Cochrane library databases were systematically analysed to search English-language articles published from inception to 31 May 2022. Studies were identified by using Me-SH terms and crossing the following terms: “obesity”, “bariatric surgery”, “left ventricular mechanics”, “left ventricular hypertrophy”, “systolic dysfunction”, “global longitudinal strain”, “echocardiography” and “STE echocardiography”. Results: The meta-analysis, including a total of 512 patients with obesity from 13 studies (follow-up 1–23 months), showed a significant GLS improvement after bariatric procedures, with standard mean difference (SMD) being 0.50 ± 0.08, CI: 0.34/0.65, p < 0.0001. Corresponding SMD value for LV ejection fraction (LVEF) was 0.15 ± 0.09, CI: −0.04/0.34, p = 0.11. A sensitivity analysis restricted to 11 studies with follow-up ≥ 6 months confirmed that GLS (SMD: 0.47 ± 0.08, CI: 0.30/0.63, p < 0.0001) but not LVEF (SMD: 0.14 ± 0.11, CI: −0.08/0.37, p = 0.21) improved after surgery. Conclusions: Our meta-analysis adds a new piece of information on the beneficial effects of bariatric surgery on LV systolic function and, more importantly, suggests that the assessment of myocardial strain should be routinely implemented for a comprehensive evaluation of cardiac functional changes associated with bariatric procedures.

Potential beneficial effects of bariatric surgery on the prevalence of kidney cancer: a national database study.

The incidence of obesity has been steadily increasing, especially in developed countries. Also, obesity is considered one of the modifiable risk factors of kidney cancer. This study aims to determine the impact of bariatric surgery-induced weight loss on the prevention of kidney cancer. Academic Hospital, United States. The National (Nationwide) Inpatient Sample (NIS) was queried for the period 2010 to 2015 for first-time kidney cancer-related hospitalization, used as a proxy for cancer incidence, in patients with a history of bariatric surgery (cases) and patients with obesity but no history of bariatric surgery (controls). Patients with a previous diagnosis of cancer were excluded from the analysis. In order to identify comparable patients, all controls had to have a body mass index ≥35 kg/m2, as per the existing qualification criteria for bariatric surgery. The International Classification of Diseases-9 codes (ICD-9) was used to identify admissions for kidney cancer. A univariate analysis was conducted to compare demographics and co-morbidities between groups. A multivariate logistic regression model was performed to assess differences between surgical and control groups and adjust for independent variables such as smoking history and family history of malignancy. All percentages and means (with confidence intervals [CIs]) were weighted. A total of 2,300,845 were included in the analysis, of which 2,004,804 controls-subjects, with a mean age of 54.4 ± .05 years, and 296,041 treatment-subjects, with a mean age of 51.9 ± .05 years. Demographics and co-morbidities, such as tobacco use, diabetes, and hypertension, were also measured. Patients with a history of bariatric surgery were significantly less likely to experience renal cancer than patients without a history of bariatric surgery, with 5935 cases in the control group and 684 in the case group (P < .0001). After a multivariate logistic regression was performed, the OR was 1.10 (95% CI: 1.02-1.22, P < .0224). Our finding suggests that bariatric surgery-induced weight loss could significantly prevent first-time kidney cancer-related hospitalizations in patients with obesity. Prospective studies are needed to confirm our findings.

Online survey on factors influencing patients' motivation to undergo bariatric surgery

SummaryGiven the worldwide increasing prevalence of severe obesity and considering the amount of scientific evidence demonstrating the beneficial effects of bariatric surgery (BS), it is surprising that only a fraction of patients with obesity undergo BS. We therefore conducted an anonymized online survey among individuals with a history of BS to understand factors influencing the deciding process leading to BS. Respondents were recruited on a voluntary basis from obesity‐related social media groups between April and June 2020. The self‐designed, non‐validated questionnaire consisted of 20 questions and was open to any participants with a history of BS. Of 851 participants who started the survey, 665 completed the questionnaire (completion rate of 78.1%). Five years after BS, still 70% of the survey‐participants were very satisfied or satisfied with the surgical result. However, the majority (73.3%) would have undergone BS earlier. The main motivation to choose BS was related to health status or quality of life. Important characteristics for a bariatric surgeon to obtain patients' trust are “taking time and listen” (74.7%), empathy (64%) and sympathy (56%). Post‐operative satisfaction with the surgical outcome was high and long‐lasting in this large cohort of BS patients. However, most participants would retrospectively have undergone BS earlier. The main reason to choose BS as treatment for their obesity were impaired physical health or reduced quality of life. Nearby location to patients' residence and availability of surgeons with empathy were decisive motives for bariatric centre selection.

Effects of obesity and weight-loss surgery shift the microbiome and impact alloimmune responses.

Obesity is a worldwide health problem with increasing rates in both children and adults. Bariatric surgery (BS) represents the only effective long-term treatment. Beneficial effects of BS may be mediated through shifts of the gut microbiome. Here, we introduce data linking the microbiome to alloimmune responses. The rapid development of microbiome sequencing technologies in addition to the availability of gnotobiotic facilities have enabled mechanistic investigations on modulations of alloimmune responses through microbiomes. BS has been shown to improve comorbidities and chronic inflammation caused by obesity. Changes in microbiota and microbiota-related metabolites may play a role. Patients either listed or having received a transplant have undergone weight loss surgery, thus allowing to dissect mechanisms of microbial shifts to alloimmunity. Weight loss and BS have the potential to improve transplant outcomes by ameliorating alloimmune responses. Those effects may be carried out through alterations of the gut microbiome.

Shifts in gut microbiota and their metabolites induced by bariatric surgery. Impact of factors shaping gut microbiota on bariatric surgery outcomes.

Evidence suggests that bariatric surgery alters gut microbiota, although its impact at compositional and functional level is not well described. In this review, the most relevant findings, mainly described in Roux-en-Y gastric bypass and sleeve gastrectomy, are outlined. Although the number of studies has increased in the last years, conclusive assertions cannot be elaborated. An issue to address is to know the influence of these alterations on host metabolism and the contribution of gut microbiota derived metabolites. New lines of research have been focusing on analysing gut microbiota functionality rather than evaluating changes at compositional level, and the functions of gut microbiota metabolites in host metabolism, what will bring more relevant information about the influence of gut microbiota in bariatric surgery outcomes. Personalized medicine, because of the predictive value of gut microbiota, is another promising field. The possibility of a specific gut microbiota pattern that could predict type 2 diabetes remission or weight loss failure after bariatric surgery is a matter of great interest. However, little is known about how gut microbiota manipulation could contribute to the beneficial effects of bariatric surgery. Peri-operative antibiotics prophylaxis or probiotic supplementation early after surgery, are strategies barely studied so far, and could constitute a novel tool in the management of weight loss and metabolic profile improvement after surgery.

Bariatric surgery and the liver-Mechanisms, benefits, and risks.

The prevalence of obesity and metabolic diseases such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) has risen dramatically over the past decades. At present, bariatric surgery is the most effective treatment for this global health problem, through effects on food intake, gut hormone secretion, metabolic signaling pathways, and adipose tissue dysfunction. The liver occupies a central role in carbohydrate, protein, and lipid metabolism. Notably, a reduction in hepatic fat content and an improvement in hepatic insulin resistance are among the earliest beneficial effects of bariatric surgery, which has therefore emerged as an attractive treatment option for NAFLD. However, as the scope and popularity of weight loss surgery have expanded, new questions have arisen regarding its safety in patients with liver cirrhosis, the outcome of liver transplantation in patients with a history of bariatric surgery, and over incidental reports of liver failure following surgery. Studies in humans and rodents have also linked bariatric surgery to an increased risk of developing alcohol use disorder, a major risk factor for liver disease. This review integrates data from clinical and translational research to delineate both the beneficial impact of bariatric surgery on the liver and the potential risks involved.

Effect of bariatric surgery on fatty liver disease in obese patients: A prospective one year follow-up study

Non-alcoholic fatty liver disease (NAFLD), often associated with obesity and metabolic syndrome, manifests itself as steatosis, hepatic fibrosis, cirrhosis, or even end-stage liver disease. NAFLD causes inflammation, insulin resistance and cardiovascular complications. The current study aimed to evaluate the beneficial effects of bariatric surgery on biochemical parameters of hepatic functions in obese patients by comparing them before and one-year after the surgery. A total of 72 morbidly obese patients underwent bariatric surgery between 2016 and 2018. The incidence of diabetes mellitus in this group was 29%, median body weight was 124.5 kg (109.0-140.0) and mean body mass index (BMI) was 44.38 ± 6.770 kg/m2. The used surgical procedures included gastric bypass, sleeve gastrectomy, laparoscopic gastric plication, and single anastomosis duodeno-ileal bypass-sleeve gastrectomy. Biochemical parameters including ALT/AST ratio (AAR), NAFLD fibrosis score (NFS), hepatic fibrosis index (FIB-4) and Fatty Liver Index (FLI) were evaluated in all patients at the time of surgery and one year after the intervention. Significant improvement after the intervention was observed in 64 patients. A significant reduction in body weight (P<0.0001), waist circumference (P<0.0001), and body mass index (P<0.0001) were observed. NAFLD liver fibrosis index changed significantly (P<0.0001), suggesting a trend of improvement from advanced fibrosis towards stages 0-2. The FIB-4 fibrosis index indicated significant improvement (P=0.0136). Besides, a significant decline in hepatic steatosis (P<0.0001) was observed after bariatric surgery as compared to the pre-surgery fatty liver conditions. Among the strategies to overcome NAFLD-associated impediments, bariatric surgery can be considered effective in reducing obesity and metabolic co-morbidities. ClinicalTrials.gov (NCT04569396).

Abstract PS17-29: Surgically induced weight loss corrects obesity associated tumor progression and improves responsiveness to immunotherapy

Abstract Background: Obesity leads to a higher risk of cancer invasion, metastases, recurrence, mortality, and impaired therapeutic response through various mechanisms. One of these mechanisms is microenvironment dysfunction, where changes in immune cells, microbes, metabolites, and growth factors contribute to tumor aggressiveness. We study obesity-induced changes to the tumor microenvironment in Triple Negative Breast Cancer (TNBC), an aggressive subtype associated with obesity. The goal to compare tumor progression in lean vs. obese vs. weight loss manipulations to identify causal and targetable pathways associated with reprogramming the tumor microenvironment. Clinically, bariatric surgery induced weight loss reduced the risk of BC, with the greatest benefit detected in pre-menopausal patients with ER- tumors, like TNBC. We hypothesize surgically-induced weight loss will diminish obesity-associated tumor progression. Methods: To study weight gain and loss that best mimics human adiposity, we utilized obesogenic C57BL/6 females with a syngeneic orthotopic transplant of TNBC cells. Female mice placed on a high fat diet (HFD) at weaning became obese compared to mice on a low fat diet (LFD). After 16 weeks on an HFD diet, mice underwent the bariatric surgery Vertical Sleeve Gastrectomy (VSG). The VSG resulted in reduced body weight, adiposity, and correction of metabolic profiles compared to obese mice. Two weeks post-surgery, TNBC cells were OT into the mammary fat. Results: As expected, tumor growth was increased in obese mice compared to lean. Importantly, surgical weight loss rescued obese tumor progression. We identified key changes in tumor infiltrating of immune cells that could be responsible for the beneficial effects of bariatric surgery on tumor progression. We then exploited these changes with immunotherapy, which was uniquely effective in mice that underwent bariatric surgery. Conclusions: In conclusion obesity promotes a pro-tumor microenvironment, that can be corrected through surgically induced weight loss. Citation Format: Laura Sipe, Mehdi Chaib, Emily B Korba, Mary C Lovely, Jared C Clements, Neena A John, Ajeeth K Pingili, Joseph F Pierre, Liza Makowski. Surgically induced weight loss corrects obesity associated tumor progression and improves responsiveness to immunotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-29.

Toward a Medical Gastric Bypass: Chronic Feeding Studies With Liraglutide + PYY3-36 Combination Therapy in Diet-Induced Obese Rats.

BackgroundCombination therapies of anorectic gut hormones partially mimic the beneficial effects of bariatric surgery. Thus far, the effects of a combined chronic systemic administration of Glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine 3-36 (PYY3-36) have not been directly compared to Roux-en-Y gastric bypass (RYGB) in a standardized experimental setting.MethodsHigh-fat diet (HFD)-induced obese male Wistar rats were randomized into six treatment groups: (1) RYGB, (2) sham-operation (shams), (3) liraglutide, (4) PYY3-36, (5) PYY3-36+liraglutide (6), saline. Animals were kept on a free choice high- and low-fat diet. Food intake, preference, and body weight were measured daily for 4 weeks. Open field (OP) and elevated plus maze (EPM) tests were performed.ResultsRYGB reduced food intake and achieved sustained weight loss. Combined PYY3-36+liraglutide treatment led to similar and plateaued weight loss compared to RYGB. Combined PYY3-36+liraglutide treatment was superior to PYY3-36 (p ≤ 0.0001) and liraglutide (p ≤ 0.05 or p ≤ 0.01) mono-therapy. PYY3-36+liraglutide treatment and RYGB also reduced overall food intake and (less pronounced) high-fat preference compared to controls. The animals showed no signs of abnormal behavior in OF or EPM.ConclusionsLiraglutide and PYY3-36 combination therapy vastly mimics reduced food intake, food choice and weight reducing benefits of RYGB.

Benefits of Bariatric Surgery Prior to SARS‐CoV‐2 Infection in Modulating the Response to COVID‐19

As of October 2020, the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), responsible for Coronavirus Disease 2019 (COVID-19), has infected over 33million individuals and killed over one million people worldwide. (https://coronavirus.jhu.edu/map.html accessed October 1 2020) Obesity and its complications are linked to severe forms of COVID-19, favouring an increased hospitalization and mortality rate. Despite being the gold-standard for the treatment of selected individuals with severe obesity, there is scarce information on whether or not bariatric surgery modifies the prognosis of people living with obesity in the current COVID-19 pandemic. Bel Lassen and colleagues have carried out the first study with a high number of patients in their sample, bringing light into this area of uncertainty. The authors provide evidence of the importance of diabetes itself as a risk factor for severe COVID-19.

Current Issues in Bariatric Surgery for Adolescents with Severe Obesity: Durability, Complications, and Timing of Intervention

Conventional nonsurgical management of severe obesity in the pediatric population and adolescents has focused on a multidisciplinary approach involving diet, exercise, behavioral modification, and to some extent, pharmaceuticals. Although nonsurgical strategies provide a certain degree of effective weight reduction, most of the severely obese adolescents suffer from a high relapse rate. In recent studies, long-term outcomes of bariatric surgery for severely obese adolescents have shown sustainable effects on weight loss and resolution of related comorbidities, such as hypertension and type 2 diabetes mellitus in this vulnerable age group. Notably, the role and practical benefits of bariatric surgery as a multidisciplinary therapeutic approach to adolescent obesity is gaining attention and acceptance. However, a surgical approach has many obstacles that prevent the timely evaluation and optimal intervention for adolescent obesity and its comorbidities. In the present review, the latest data on long-term outcomes after bariatric surgery for severely obese adolescents in terms of durability, effects on metabolic risk factors, complications, and optimal timing were summarized. The results showed the sustainability of weight loss and comorbidity resolution in adolescents following bariatric surgery. In addition, earlier surgery in patients without an extremely high body mass index increases the likelihood of a healthier life in adulthood. This review can help clarify the beneficial effects of bariatric surgery on weight reduction and resolution of comorbidities in severely obese adolescents and remove the barriers to referral of adolescents for bariatric surgery.

Metabolic and Endocrine Consequences of Bariatric Surgery.

Obesity is one of the most serious worldwide epidemics of the twenty-first century according to the World Health Organization. Frequently associated with a number of comorbidities, obesity threatens and compromises individual health and quality of life. Bariatric surgery (BS) has been demonstrated to be an effective treatment to achieve not only sustained weight loss but also significant metabolic improvement that goes beyond mere weight loss. The beneficial effects of BS on metabolic traits are so widely recognized that some authors have proposed BS as metabolic surgery that could be prescribed even for moderate obesity. However, most of the BS procedures imply malabsorption and/or gastric acid reduction which lead to nutrient deficiency and, consequently, further complications could be developed in the long term. In fact, BS not only affects metabolic homeostasis but also has pronounced effects on endocrine systems other than those exclusively involved in metabolic function. The somatotropic, corticotropic, and gonadal axes as well as bone health have also been shown to be affected by the various BS procedures. Accordingly, further consequences and complications of BS in the long term in systems other than metabolic system need to be addressed in large cohorts, taking into account each bariatric procedure before making generalized recommendations for BS. In this review, current data regarding these issues are summarized, paying special attention to the somatotropic, corticotropic, gonadal axes, and bone post-operative health.

Combined loss of GLP-1R and Y2R does not alter progression of high-fat diet-induced obesity or response to RYGB surgery in mice

ObjectiveUnderstanding the mechanisms underlying the remarkable beneficial effects of gastric bypass surgery is important for the development of non-surgical therapies or less invasive surgeries in the fight against obesity and metabolic disease. Although the intestinal L-cell hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine–tyrosine (PYY) have attracted the most attention, direct tests in humans and rodents with pharmacological blockade or genetic deletion of either the GLP1-receptor (GLP1R) or the Y2-receptor (Y2R) were unable to confirm their critical roles in the beneficial effects gastric bypass surgery on body weight and glucose homeostasis. However, new awareness of the power of combinatorial therapies in the treatment of metabolic disease would suggest that combined blockade of more than one signaling pathway may be necessary to reverse the beneficial effects of bariatric surgery. MethodsThe metabolic effects of high-fat diet and the ability of Roux-en-Y gastric bypass surgery to lower food intake and body weight, as well as improve glucose handling, was tested in GLP1R and Y2R-double knockout (GLP1RKO/Y2RKO) and C57BL6J wildtype (WT) mice. ResultsGLP1RKO/Y2RKO and WT mice responded similarly for up to 20 weeks on high-fat diet and 16 weeks after RYGB. There were no significant differences in loss of body and liver weight, fat mass, reduced food intake, relative increase in energy expenditure, improved fasting insulin, glucose tolerance, and insulin tolerance between WT and GLP1RKO/Y2RKO mice after RYGB. ConclusionsCombined loss of GLP1R and Y2R-signaling was not able to negate or attenuate the beneficial effects of RYGB on body weight and glucose homeostasis in mice, suggesting that a larger number of signaling pathways is involved or that the critical pathway has not yet been identified.

The Importance of the Microbiome in Bariatric Surgery: a Systematic Review

Bariatric surgery results in sustained weight loss, improvement of metabolic and hormonal changes, and reduction of comorbidities in obese patients. However, beneficial effects of bariatric surgery are not solely explained by restriction and malabsorption induced by surgery itself. Changes in the microbiome might play a role in this mechanism. A systematic review was performed in which 21 studies were included. The microbiome was affected by surgery and profound changes occurred in the first year of follow-up. An increase in Bacteroides and Proteobacteria and a decrease in Firmicutes were observed postoperatively in most studies. These changes were associated with weight loss. Bariatric surgery induces profound changes in the microbiome. This may be related to the beneficial effect of bariatric surgery on comorbidities associated with obesity.

The PYY/Y2R-Deficient Mouse Responds Normally to High-Fat Diet and Gastric Bypass Surgery.

Background/Goals: The gut hormone peptide YY (PYY) secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight. Methods: Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype (WT) mice made obese on high-fat diet. Results: Both male and female Y2RKO mice responded normally to low- and high-fat diet in terms of body weight, body composition, fasting levels of glucose and insulin, as well as glucose and insulin tolerance for up to 30 weeks of age. Contrary to expectations, obese Y2RKO mice also responded similarly to RYGB compared to WT mice for up to 20 weeks after surgery, with initial hypophagia, sustained body weight loss, and significant improvements in fasting insulin, glucose tolerance, insulin resistance (HOMA-IR), and liver weight compared to sham-operated mice. Furthermore, non-surgical Y2RKO mice weight-matched to RYGB showed the same improvements in glycemic control as Y2RKO mice with RYGB that were similar to WT mice. Conclusions: PYY signaling through Y2R is not required for the normal appetite-suppressing and body weight-lowering effects of RYGB in this global knockout mouse model. Potential compensatory adaptations of PYY signaling through other receptor subtypes or other gut satiety hormones such as glucagon-like peptide-1 (GLP-1) remain to be investigated.

Targeting Bile Acid-Activated Receptors in Bariatric Surgery.

Bariatric surgical procedures, including Roux-en-Y gastric bypass and vertical sleeve gastrectomy, are currently the most effective clinical approaches to achieve a significant and sustainable weight loss. Bariatric surgery also concomitantly improves type 2 diabetes and other metabolic diseases such as nonalcoholic steatohepatitis, cardiovascular diseases, and hyperlipidemia. However, despite the recent exciting progress in the understanding how bariatric surgery works, the underlying molecular mechanisms of bariatric surgery remain largely unknown. Interestingly, bile acids are emerging as potential signaling molecules to mediate the beneficial effects of bariatric surgery. In this review, we summarize the recent findings on bile acids and their activated receptors in mediating the beneficial metabolic effects of bariatric surgery. We also discuss the potential to target bile acid-activated receptors in order to treat obesity and other metabolic diseases.