Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity.

White adipose tissue (WAT) is an essential regulator of energy storage and systemic metabolic homeostasis. Regulatory networks consisting of immune and structural cells are necessary to maintain WAT metabolism, which can become impaired during obesity in mammals. Using single-cell transcriptomics and flow cytometry, we unveil a large-scale comprehensive cellular census of the stromal vascular fraction of healthy lean and obese human WAT. We report new subsets and developmental trajectories of adipose-resident innate lymphoid cells, dendritic cells and monocyte-derived macrophage populations that accumulate in obese WAT. Analysis of cell-cell ligand-receptor interactions and obesity-enriched signaling pathways revealed a switch from immunoregulatory mechanisms in lean WAT to inflammatory networks in obese WAT. These results provide a detailed and unbiased cellular landscape of homeostatic and inflammatory circuits in healthy human WAT.

Food Intake and Eating Behavior After Bariatric Surgery.

Obesity is an escalating global chronic disease. Bariatric surgery is a very efficacious treatment for obesity and its comorbidities. Alterations to gastrointestinal anatomy during bariatric surgery result in neurological and physiological changes affecting hypothalamic signaling, gut hormones, bile acids, and gut microbiota, which coalesce to exert a profound influence on eating behavior. A thorough understanding of the mechanisms underlying eating behavior is essential in the management of patients after bariatric surgery. Studies investigating candidate mechanisms have expanded dramatically in the last decade. Herein we review the proposed mechanisms governing changes in eating behavior, food intake, and body weight after bariatric surgery. Additive or synergistic effects of both conditioned and unconditioned factors likely account for the complete picture of changes in eating behavior. Considered application of strategies designed to support the underlying principles governing changes in eating behavior holds promise as a means of optimizing responses to surgery and long-term outcomes.

Bariatric surgery for spontaneous ovulation in women living with polycystic ovary syndrome: the BAMBINI multicentre, open-label, randomised controlled trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Obesity exacerbates the reproductive complications of PCOS; however, the management of obesity in women with PCOS remains a large unmet clinical need. Observational studies have indicated that bariatric surgery could improve the rates of ovulatory cycles and prospects of fertility; however, the efficacy of surgery on ovulation rates has not yet been compared with behavioural modifications and medical therapy in a randomised trial. The aim of this study was to compare the safety and efficacy of bariatric surgery versus medical care on ovulation rates in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. METHODS: In this multicentre, open-label, randomised controlled trial, 80 women older than 18 years, with a diagnosis of PCOS based on the 2018 international evidence-based guidelines for assessing and managing PCOS, and a BMI of 35 kg/m2 or higher, were recruited from two specialist obesity management centres and via social media. Participants were randomly assigned at a 1:1 ratio to either vertical sleeve gastrectomy or behavioural interventions and medical therapy using a computer-generated random sequence (PLAN procedure in SAS) by an independent researcher not involved with any other aspect of the clinical trial. The median age of the entire cohort was 31 years and 79% of participants were White. The primary outcome was the number of biochemically confirmed ovulatory events over 52 weeks, and was assessed using weekly serum progesterone measurements. The primary endpoint included the intention-to-treat population and safety analyses were per-protocol population. This study is registered with the ISRCTN registry (ISRCTN16668711). FINDINGS: Participants were recruited from Feb 20, 2020 to Feb 1, 2021. 40 participants were assigned to each group and there were seven dropouts in the medical group and ten dropouts in the surgical group. The median number of ovulations was 6 (IQR 3·5-10·0) in the surgical group and 2 (0·0-4·0) in the medical group. Women in the surgical group had 2.5 times more spontaneous ovulations compared with the medical group (incidence rate ratio 2·5 [95% CI 1·5-4·2], p<0·0007). There were more complications in the surgical group than the medical group, although without long-term sequelae. There were 24 (66·7%) adverse events in the surgical group and 12 (30·0%) in the medical group. There were no treatment-related deaths. INTERPRETATION: Bariatric surgery was more effective than medical care for the induction of spontaneous ovulation in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. Bariatric surgery could, therefore, enhance the prospects of spontaneous fertility in this group of women. FUNDING: The Jon Moulton Charity Trust.

Short-term effects of obesity surgery versus low-energy diet on body composition and tissue-specific glucose uptake: a randomised clinical study using whole-body integrated 18F-FDG-PET/MRI.

AIMS/HYPOTHESIS: Obesity surgery (OS) and diet-induced weight loss rapidly improve insulin resistance. We aim to investigate the impact of either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with a diet low in energy (low-calorie diet; LCD) on body composition, glucose control and insulin sensitivity, assessed both at the global and tissue-specific level in individuals with obesity but not diabetes. METHODS: In this parallel group randomised controlled trial, patients on a waiting list for OS were randomised (no blinding, sealed envelopes) to either undergo surgery directly or undergo an LCD before surgery. At baseline and 4 weeks after surgery (n=15, 11 RYGB and 4 SG) or 4 weeks after the start of LCD (n=9), investigations were carried out, including an OGTT and hyperinsulinaemic-euglycaemic clamps during which concomitant simultaneous whole-body [18F]fluorodeoxyglucose-positron emission tomography (PET)/MRI was performed. The primary outcome was HOMA-IR change. RESULTS: One month after bariatric surgery and initiation of LCD, both treatments induced similar reductions in body weight (mean ± SD: -7.7±1.4 kg and -7.4±2.2 kg, respectively), adipose tissue volume (7%) and liver fat content (2% units). HOMA-IR, a main endpoint, was significantly reduced following OS (-26.3% [95% CI -49.5, -3.0], p=0.009) and non-significantly following LCD (-20.9% [95% CI -58.2, 16.5). For both groups, there were similar reductions in triglycerides and LDL-cholesterol. Fasting plasma glucose and insulin were also significantly reduced only following OS. There was an increase in glucose AUC in response to an OGTT in the OS group (by 20%) but not in the LCD group. During hyperinsulinaemia, only the OS group showed a significantly increased PET-derived glucose uptake rate in skeletal muscle but a reduced uptake in the heart and abdominal adipose tissue. Both liver and brain glucose uptake rates were unchanged after surgery or LCD. Whole-body glucose disposal and endogenous glucose production were not significantly affected. CONCLUSIONS/INTERPRETATION: The short-term metabolic effects seen 4 weeks after OS are not explained by loss of body fat alone. Thus OS, but not LCD, led to reductions in fasting plasma glucose and insulin resistance as well as to distinct changes in insulin-stimulated glucose fluxes to different tissues. Such effects may contribute to the prevention or reversal of type 2 diabetes following OS. Moreover, the full effects on whole-body insulin resistance and plasma glucose require a longer time than 4 weeks. TRIAL REGISTRATION: ClinicalTrials.gov NCT02988011 FUNDING: This work was supported by AstraZeneca R&D, the Swedish Diabetes Foundation, the European Union's Horizon Europe Research project PAS GRAS, the European Commission via the Marie Sklodowska Curie Innovative Training Network TREATMENT, EXODIAB, the Family Ernfors Foundation, the P.O. Zetterling Foundation, Novo Nordisk Foundation, the Agnes and Mac Rudberg Foundation and the Uppsala University Hospital ALF grants.

Bariatric surgery decreases the capacity of plasma from obese asthmatic subjects to augment airway epithelial cell proinflammatory cytokine production.

Obesity is a risk factor for asthma. Individuals with asthma and obesity often have poor asthma control and do not respond as well to therapies such as inhaled corticosteroids and long-acting bronchodilators. Weight loss improves asthma control, with a 5%-10% loss in body mass necessary and sufficient to lead to clinically relevant improvements. Preclinical studies have demonstrated the pathogenic contribution of adipocytes from obese mice to the augmented production of proinflammatory cytokines from airway epithelial cells and the salutary effects of diet-induced weight loss to decrease these consequences. However, the effects of adipocyte-derived products on airway epithelial function in human obesity remain incompletely understood. We utilized samples collected from a 12-mo longitudinal study of subjects with obesity undergoing weight loss (bariatric) surgery including controls without asthma and subjects with allergic and nonallergic obese asthma. Visceral adipose tissue (VAT) samples were collected during bariatric surgery and from recruited normal weight controls without asthma undergoing elective abdominal surgery. Human bronchial epithelial (HBEC3-KT) cells were exposed to plasma or conditioned media from cultured VAT adipocytes with or without agonists. Human bronchial smooth muscle (HBSM) cells were similarly exposed to adipocyte-conditioned media. Proinflammatory cytokines were augmented in supernatants from HBEC3-KT cells exposed to plasma as compared with subsequent visits. Whereas exposure to obese adipocyte-conditioned media induced proinflammatory responses, there were no differences between groups in both HBEC3-KT and HBSM cells. These data show that bariatric surgery and subsequent weight loss beneficially change the circulating factors that augment human airway epithelial and bronchial smooth muscle cell proinflammatory responses.NEW & NOTEWORTHY This longitudinal study following subjects with asthma and obesity reveals that weight loss following bariatric surgery decreases the capacity for plasma to augment proinflammatory cytokine secretion by human bronchial epithelial cells, implicating that circulating but not adipocyte-derived factors are important modulators in obese asthma.

Metabolic outcomes in obese mice undergoing one-anastomosis gastric bypass (OAGB) with a long or a short biliopancreatic limb.

One-anastomosis gastric bypass (OAGB) has gained importance as a simple, safe, and effective operation to treat morbid obesity. We previously found that Roux-en-Y gastric bypass surgery with a long compared with a short biliopancreatic limb (BPL) leads to improved weight loss and glucose tolerance in obese mice. However, it is not known whether a long BPL in OAGB surgery also results in beneficial metabolic outcomes. Five-week-old male C57BL/6J mice fed a high-fat diet (HFD) for 8 weeks underwent OAGB surgery with defined BPL lengths (5.5 cm distally of the duodenojejunal junction for short and 9.5 cm for long BPL), or sham surgery combined with caloric restriction. Weight loss, glucose tolerance, obesity-related comorbidities, endocrine effects, gut microbiota, and bile acids were assessed. Total weight loss was independent of the length of the BPL after OAGB surgery. However, a long BPL was associated with lower glucose-stimulated insulin on day 14, and an improved glucose tolerance on day 35 after surgery. Moreover, a long BPL resulted in reduced total cholesterol, while there were no differences in the resolution of metabolic dysfunction-associated steatotic liver disease (MASLD) and adipose tissue inflammation. Tendencies of an attenuated hypothalamic-pituitary-adrenal (HPA) axis and aldosterone were present in the long BPL group. With both the short and long BPL, we found an increase in primary conjugated bile acids (pronounced in long BPL) along with a loss in bacterial Desulfovibrionaceae and Erysipelotrichaceae and simultaneous increase in Akkermansiaceae, Sutterellaceae, and Enterobacteriaceae. In summary, OAGB surgery with a long compared with a short BPL led to similar weight loss, but improved glucose metabolism, lipid, and endocrine outcomes in obese mice, potentially mediated through changes in gut microbiota and related bile acids. Tailoring the BPL length in humans might help to optimize metabolic outcomes after bariatric surgery.NEW & NOTEWORTHY Weight loss following OAGB surgery in obese mice was not influenced by BPL length, but a longer BPL was associated with improved metabolic outcomes, including glucose and lipid homeostasis. These changes could be mediated by bile acids upon altered gut microbiota. Further validation of these findings is required through a randomized human study.

Endoscopic Approaches to Obesity Management.

The field of endoscopic bariatric and metabolic therapy has rapidly evolved from offering endoscopic treatment of weight regain following bariatric surgery to providing primary weight loss options as alternatives to pharmacologic and surgical interventions. Gastric devices and remodeling procedures were initially designed to work through a mechanism of volume restriction, leading to earlier satiety and reduced caloric intake. As the field continues to grow, small bowel interventions are evolving that may have some effect on weight loss but focus on the treatment of obesity-related comorbidities. Future implementation of combination therapy that utilizes both gastric and small bowel interventions offers an exciting option to further augment weight loss and alleviate metabolic disease. This review considers gastric devices and techniques including space-occupying intragastric balloons, aspiration therapy, endoscopic tissue suturing, and plication interventions, followed by a review of small bowel interventions including endoluminal bypass liners, duodenal mucosal resurfacing, and endoscopically delivered devices to create incisionless anastomoses.

Contemporary medical, device, and surgical therapies for obesity in adults.

The goal of obesity management is to improve health. Sustained weight loss of more than 10% overall bodyweight improves many of the complications associated with obesity (eg, prevention and control of type 2 diabetes, hypertension, fatty liver disease, and obstructive sleep apnoea), as well as quality of life. Maintenance of weight loss is the major challenge of obesity management. Like all chronic diseases, managing obesity requires a long-term, multimodal approach, taking into account each individual's treatment goals, and the benefit and risk of different therapies. In conjunction with lifestyle interventions, anti-obesity medications and bariatric surgery improve the maintenance of weight loss and associated health gains. Most available anti-obesity medications act on central appetite pathways to reduce hunger and food reward. In the past 5 years, therapeutic advances have seen the development of targeted treatments for monogenic obesities and a new generation of anti-obesity medications. These highly effective anti-obesity medications are associated with weight losses of more than 10% of overall bodyweight in more than two-thirds of clinical trial participants. Long-term data on safety, efficacy, and cardiovascular outcomes are awaited. Long-term studies have shown that bariatric surgical procedures typically lead to a durable weight loss of 25% and rapid, sustained improvements in complications of obesity, although they have not yet been compared with new-generation highly effective anti-obesity medications. Further work is required to determine optimal patient-specific treatment strategies, including combinations of lifestyle interventions, anti-obesity medications, endoscopic and bariatric surgical procedures, and to ensure equitable access to effective treatments.

Do patients with obesity undergoing bariatric surgery modify their objectively measured physical activity? A systematic review and meta-analysis.

BACKGROUND: Obesity is a chronic disease associated with adverse outcomes and its prevalence is increasing, which makes it a concern. One of the obesity treatment options is bariatric surgery, which effectively reduces calorie absorption and total body mass, but its effects on physical activity (PA) levels need to be clarified, considering the protective effect of the PA against cardiovascular disease, independently of the weight loss alone. OBJECTIVES: To carry out a systematic review and meta-analysis of observational studies that evaluated PA in pre- and post-bariatric surgery periods through objective evaluation. METHODS: A systematic search was carried out following the PRISMA criteria of studies with adult individuals who underwent bariatric surgery and were objectively evaluated for PA pre- and post-surgery. Studies with interventions were excluded. RESULTS: A total of 419 records were found, and after excluding duplicates and applying the eligibility criteria, 10 studies remained. This meta-analysis found a significant increase in the steps by day (MD = 1340; 95% CI = 933.90; 1745.35, p < 0.001) and the light physical activity level (MD = 16.8 min/day; 95% CI = 2.60; 30.98, p = 0.02), but not in moderate to vigorous physical activity (MD = 0.24; 95% CI = -0.08; 1.57, p = 0.92). CONCLUSIONS: Patients undergoing bariatric surgery increased their steps by day and light physical activity but did not increase moderate to vigorous physical activity.

Transcriptional and epigenetic changes after dietary and surgical weight loss interventions in an animal model of obesity.

BACKGROUND: Identifying determinants that can predict response to weight loss interventions is imperative for optimizing therapeutic benefit. We aimed to identify changes in DNA methylation and mRNA expression of a subset of target genes following dietary and surgical interventions in high-fat-diet (HFD)-induced obese rats. METHODS: Forty-two adult Wistar Han male rats were divided into two groups: control rats (n = 7) and obese rats (n = 28), fed a HFD for 10 weeks (t10). Obese rats were randomly subdivided into five intervention groups (seven animals per group): (i) HFD; (ii) very-low-calorie diet (VLCD); (iii) sham surgery, and (iv) sleeve gastrectomy (SG). At week sixteen (t16), animals were sacrificed and tissue samples were collected to analyze changes in DNA methylation and mRNA expression of the selected genes. RESULTS: By type of intervention, the surgical procedures led to the greatest weight loss. Changes in methylation and/or expression of candidate genes occurred proportionally to the effectiveness of the weight loss interventions. Leptin expression, increased sixfold in the visceral fat of the obese rats, was partially normalized after all interventions. The expression of fatty acid synthase (FASN) and monocyte chemoattractant protein 1 (MCP-1) genes, which was reduced 0.5- and 0.15-fold, respectively, in the liver tissue of obese rats, were completely normalized after weight loss interventions, particularly after surgical interventions. The upregulation of FASN and MCP-1 gene expression was accompanied by a significant reduction in promoter methylation, up to 0.5-fold decrease in the case of the FASN (all intervention groups) and a 0.8-fold decrease in the case of the MCP-1 (SG group). CONCLUSIONS: Changes in tissue expression of specific genes involved in the pathophysiological mechanisms of obesity can be significantly attenuated following weight loss interventions, particularly surgery. Some of these genes are regulated by epigenetic mechanisms.

Change in abdominal obesity after colon cancer surgery - effects of left-sided and right-sided colonic resection.

BACKGROUND: Excess abdominal visceral adipose tissue (VAT) is associated with metabolic diseases and poor survival in colon cancer (CC). We assessed the impact of different types of CC surgery on changes in abdominal fat depots. MATERIAL AND METHODS: Computed tomography (CT)-scans performed preoperative and 3 years after CC surgery were analyzed at L3-level for VAT, subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) areas. We assessed changes in VAT, SAT, TAT and VAT/SAT ratio after 3 years and compared the changes between patients who had undergone left-sided and right-sided colonic resection in the total population and in men and women separately. RESULTS: A total of 134 patients with stage I-III CC undergoing cancer surgery were included. Patients who had undergone left-sided colonic resection had after 3 years follow-up a 5% (95% CI: 2-9%, p < 0.01) increase in abdominal VAT, a 4% (95% CI: 2-6%, p < 0.001) increase in SAT and a 5% increase (95% CI: 2-7%, p < 0.01) in TAT. Patients who had undergone right-sided colonic resection had no change in VAT, but a 6% (95% CI: 4-9%, p < 0.001) increase in SAT and a 4% (95% CI: 1-7%, p < 0.01) increase in TAT after 3 years. Stratified by sex, only males undergoing left-sided colonic resection had a significant VAT increase of 6% (95% CI: 2-10%, p < 0.01) after 3 years. CONCLUSION: After 3 years follow-up survivors of CC accumulated abdominal adipose tissue. Notably, those who underwent left-sided colonic resection had increased VAT and SAT, whereas those who underwent right-sided colonic resection demonstrated solely increased SAT.

Weight loss in adult male Wistar rats by Roux-en-Y gastric bypass is primarily explained by caloric intake reduction and presurgery body weight.

Diets varying in macronutrient composition, energy density, and/or palatability may cause differences in outcome of bariatric surgery. In the present study, rats feeding a healthy low-fat (LF) diet or an obesogenic high-fat/sucrose diet (HF/S) were either subjected to Roux-en-Y gastric bypass surgery (RYGB) or sham surgery, and weight loss trajectories and various energy balance parameters were assessed. Before RYGB, rats eating an HF/S (n = 14) diet increased body weight relative to rats eating an LF diet (n = 20; P < 0.01). After RYGB, absolute weight loss was larger in HF/S (n = 6) relative to LF feeding (n = 6) rats, and this was associated with reduced cumulative energy intake (EI; P < 0.05) and increased locomotor activity (LA; P < 0.05-0.001), finally leading to similar levels of reduced body fat content in HF/S and LF rats 3 wk after surgery. Regression analysis revealed that variation in RYGB-induced body weight loss was best explained by models including 1) postoperative cumulative EI and preoperative body weight (R2 = 0.87) and 2) postoperative cumulative EI and diet (R2 = 0.79), each without significant contribution of LA. Particularly rats on the LF diet became transiently more hypothermic and circadianally arrhythmic following RYGB (i.e., indicators of surgery-associated malaise) than HF/S feeding rats. Our data suggest that relative to feeding an LF diet, continued feeding an HF/S diet does not negatively impact recovery from RYGB surgery, yet it promotes RYGB-induced weight loss. The RYGB-induced weight loss is primarily explained by reduced cumulative EI and higher preoperative body weight, leading to comparably low levels of body fat content in HF/S and LF feeding rats.NEW & NOTEWORTHY Relative to feeding an LF diet, continued feeding an HF/S diet does not negatively impact recovery from RYGB surgery in rats. Relative to feeding an LF diet, continued feeding an HF/S diet promotes RYGB-induced weight loss. The RYGB-induced weight loss is primarily explained by reduced cumulative EI and higher preoperative body weight, leading to comparably low levels of body fat content in HF/S and LF feeding rats.

Biliopancreatic diversion for severe obesity: long-term weight maintenance and occurrence of nutritional complications are two facets of the same coin.

BACKGROUND: Despite the widespread clinical use of hypoabsorptive metabolic bariatric surgery, very long-term outcomes are still lacking. The aim of the study was to assess the long-term safety and efficacy of biliopancreatic diversion at 30 years in patients with class 3 obesity (BMI over 40 kg/m2). METHODS: This retrospective single-centre study used data from a prospectively collected database on a sample of consecutive patients submitted to biliopancreatic diversion with a minimum follow-up of 30 years. Outcomes assessed included overall survival, long-term weight loss and weight maintenance, remission of obesity-related co-morbidities, and short- and long-term surgical and/or nutritional or metabolic complications. RESULTS: Among 199 consecutive patients (136 female, 63 male) who had surgery between November 1992 and April 1994, the mean age at operation was 38 (range 14-69) years and mean preoperative BMI was 48.7 (32.0-74.3) kg/m2. At baseline, 91 of 199 patients (45.7%) had type 2 diabetes. At 20 and 30 years, 122 (61%) and 38 (19%) of the 199 patients respectively were available for follow-up. At 30 years, the overall mortality rate was 12% (23 of 199). Surgical complications were concentrated in the short-term follow-up, whereas nutritional or metabolic complications increased progressively over time. A nutritional complication was diagnosed in 73 of 122 patients (60%) at 20 years and 28 of 38 (74%) at 30 years. Weight loss and glycaemic control were maintained throughout the follow-up; mean % total weight loss was 32.8 (range 14.1-50.0) at 1 year and 37.7 (range 16.7-64.8) at 30 years. One patient presented with recurrence of type 2 diabetes at 20 and 30 years; there were no patients with new-onset type 2 diabetes. CONCLUSION: Biliopancreatic diversion leads to good and sustained weight maintenance up to 30 years with low perioperative risk, but at the cost of a high long-term prevalence of nutritional complications.

The long-term effect of bariatric/metabolic surgery versus pharmacologic therapy in type 2 diabetes mellitus patients: A systematic review and meta-analysis.

Metabolic/bariatric surgery as a treatment for obesity and related diseases, such as type 2 diabetes mellitus (T2DM), has been increasingly recognised in recent years. However, compared with conventional pharmacologic therapy, the long-term effect (≥ 5 years) of metabolic surgery in T2DM patients is still unclear. This study aimed to evaluate the diabetes remission rate, incidence of diabetic microvascular complications, incidence of macrovascular complications, and mortality in T2DM patients who received metabolic surgery versus pharmacologic therapy more than 5 years after the surgery. Searching the database, including PubMed, Embase, Web of Science, and Cochrane Library from the inception to recent (2024), for randomised clinical trials (RCTs) or cohort studies comparing T2DM patients treated with metabolic surgery versus pharmacologic therapy reporting on the outcomes of the diabetes remission rate, diabetic microvascular complications, macrovascular complications, or mortality over 5 years or more. A total of 15 articles with a total of 85,473 patients with T2DM were eligible for review and meta-analysis in this study. There is a significant long-term increase in diabetes remission for metabolic surgery compared with conventional medical therapy in the overall pooled estimation and RCT studies or cohort studies separately (overall: OR = 4.58, 95% CI: 1.89-11.07, P < 0.001). Significant long-term decreases were found in the pooled results of microvascular complications incidence (HR = 0.57, 95% CI: 0.41-0.78, P < 0.001), macrovascular complications incidence (HR = 0.59, 95% CI: 0.50-0.70, P < 0.001) and mortality (HR = 0.53, 95% CI: 0.53-0.79, P = 0.0018). Metabolic surgery showed more significant long-term effects than pharmacologic therapy on diabetes remission, macrovascular complications, microvascular complications incidence, and all-cause mortality in patients with T2DM using currently available evidence. More high-quality evidence is needed to validate the long-term effects of metabolic surgery versus conventional treatment in diabetes management.

Peripheral inflammation associated with depression and reduced weight loss: a longitudinal study of bariatric patients.

BACKGROUND: Research implicates inflammation in the vicious cycle between depression and obesity, yet few longitudinal studies exist. The rapid weight loss induced by bariatric surgery is known to improve depressive symptoms dramatically, but preoperative depression diagnosis may also increase the risk for poor weight loss. Therefore, we investigated longitudinal associations between depression and inflammatory markers and their effect on weight loss and clinical outcomes in bariatric patients. METHODS: This longitudinal observational study of 85 patients with obesity undergoing bariatric surgery included 41 cases with depression and 44 controls. Before and 6 months after surgery, we assessed depression by clinical interview and measured serum high-sensitivity C-reactive protein (hsCRP) and inflammatory cytokines, including interleukin (IL)-6 and IL-10. RESULTS: Before surgery, depression diagnosis was associated with significantly higher serum hsCRP, IL-6, and IL-6/10 ratio levels after controlling for confounders. Six months after surgery, patients with pre-existing depression still had significantly higher inflammation despite demonstrating similar weight loss to controls. Hierarchical regression showed higher baseline hsCRP levels predicted poorer weight loss (ß = -0.28, p = 0.01) but had no effect on depression severity at follow-up (ß = -0.02, p = 0.9). Instead, more severe baseline depressive symptoms and childhood emotional abuse predicted greater depression severity after surgery (ß = 0.81, p < 0.001; and ß = 0.31, p = 0.001, respectively). CONCLUSIONS: Depression was significantly associated with higher inflammation beyond the effect of obesity and other confounders. Higher inflammation at baseline predicted poorer weight loss 6 months after surgery, regardless of depression diagnosis. Increased inflammation, rather than depression, may drive poor weight loss outcomes among bariatric patients.

Endoscopic sleeve gastroplasty as an early tool against obesity: a multicenter international study on an overweight population.

BACKGROUND AND AIMS: Endoscopic sleeve gastroplasty (ESG) is an effective, minimally invasive gastric remodeling procedure to treat mild and moderate obesity. Early adoption of ESG may be desirable to try to halt progression of obesity, but there are few data on its efficacy and safety for overweight patients. METHODS: This was a multicenter, international, analytical case series. Six U.S., 1 Brazilian, 1 Mexican, and 1 Indian center were included. Overweight patients according to local practice undergoing ESG were considered eligible for the study. The end points were percent total weight loss (%TWL), body mass index (BMI) reduction, rate of BMI normalization, and rate of adverse events. RESULTS: One hundred eighty-nine patients with a mean age of 42.6 ± 14.1 years and a mean BMI of 27.79 ± 1.17 kg/m2 were included. All procedures were successfully accomplished, and there were 3 intraprocedural adverse events (1.5%). The mean %TWL was 12.28% ± 3.21%, 15.03% ± 5.30%, 15.27% ± 5.28%, and 14.91% ± 5.62% at 6, 12, 24, and 36 months, respectively. At 12 and 24 months, 76% and 86% of patients achieved normal BMI, with a mean BMI reduction of 4.13 ± 1.46 kg/m2 and 4.25 ± 1.58 kg/m2. There was no difference in mean %TWL in the first quartile versus the fourth quartile of BMI in any of the time points. However, the BMI normalization rate was statistically higher in the first group at 6 and 12 months (6 months, 100% vs 48.5% [P < .01]; 12 months, 86.2% vs 50% [P < .01]; 24 months, 84.6% vs 76.1% [P = .47]; 36 months, 86.3% vs 66.6% [P = .26]). CONCLUSIONS: ESG is safe and effective in treating overweight patients with high BMI normalization rates. It could help halt or delay the progression to obesity.

How best to combine liver transplantation and bariatric surgery?-Results from a global, web-based survey.

BACKGROUND AND AIMS: Obesity is a growing healthcare challenge worldwide and a significant risk factor for liver failure as seen with non-alcoholic steatohepatitis (NASH). Combining metabolic-bariatric surgery (MBS) with liver transplantation (LT) appears as attractive strategy to treat both, the underlying liver disease and obesity. However, there is an ongoing debate on best timing and patient selection. This survey was designed to explore the current treatment practice for patients with NASH and obesity worldwide. METHODS: A web-based survey was conducted in 2022 among bariatric and LT surgeons, and hepatologists from Europe, North and South America and Asia. RESULTS: The survey completion rate was 74% (145/196). The average respondents were 41-50 years (38%), male (82.1%) and had >20 years of clinical experience (42.1%). Centres with a high LT-caseload for NASH were mainly located in the USA and United Kingdom. Almost 30% have already performed a combination of LT with MBS and 49% plan to do it. A majority of bariatric surgeons prefer MBS before LT (77.2%), whereas most of LT surgeons (52%) would perform MBS during LT. Most respondents (n = 114; 80%) favour sleeve gastrectomy over other bariatric techniques. One third (n = 42; 29.4%) has an established protocol regarding MBS for LT candidates. CONCLUSION: The most experienced centres doing LT for NASH are in the USA and United Kingdom with growing awareness worldwide. Overall, a combination of MBS and LT has already been performed by a third of respondents. Sleeve gastrectomy is the bariatric technique of choice-preferably performed either before or during LT.

Construction and validation of a nomogram for predicting diabetes remission at 3 months after bariatric surgery in patients with obesity combined with type 2 diabetes mellitus.

AIM: Bariatric metabolic surgery (BMS) is a proven treatment option for patients with both obesity and type 2 diabetes mellitus (T2DM). However, there is a lack of comprehensive reporting on the short-term remission rates of diabetes, and the existing data are inadequate. Hence, this study aimed to investigate the factors that may contribute to diabetes remission (DR) in patients with obesity and T2DM, 3 months after undergoing BMS. Furthermore, our objective was to develop a risk-predicting model using a nomogram. METHODS: In total, 389 patients with obesity and T2DM, who had complete preoperative information and underwent either laparoscopic sleeve gastrectomy or laparoscopic gastric bypass surgery between January 2014 and May 2023, were screened in the Chinese Obesity and Metabolic Surgery Database. The patients were randomly divided into a training set (n = 272) and a validation set (n = 117) in a 7:3 ratio. Potential factors for DR were analysed through univariate and multivariate logistic regression analyses and then modelled using a nomogram. The model's performance was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Calibration plots were used to assess prediction accuracy and decision curve analyses were conducted to evaluate the clinical usefulness of the model. RESULTS: Glycated haemoglobin, triglycerides, duration of diabetes, insulin requirement and hypercholesterolaemia were identified as independent factors influencing DR. We have incorporated these five indicators into a nomogram, which has shown good efficacy in both the training cohort (AUC = 0.930) and validation cohort (AUC = 0.838). The calibration plots indicated that the model fits well in both the training and the validation cohorts, and decision curve analyses showed that the model had good clinical applicability. CONCLUSION: The prediction model developed in this study holds predictive value for short-term DR following BMS in patients with obesity and T2DM.

A look at duodenal mucosal resurfacing: Rationale for targeting the duodenum in type 2 diabetes.

Affecting 5%-10% of the world population, type 2 diabetes (T2DM) is firmly established as one of the major health burdens of modern society. People with T2DM require long-term therapies to reduce blood glucose, an approach that can mitigate the vascular complications. However, fewer than half of those living with T2DM reach their glycaemic targets despite the availability of multiple oral and injectable medications. Adherence and access to medications are major barriers contributing to suboptimal diabetes treatment. The gastrointestinal tract has recently emerged as a target for treating T2DM and altering the underlying disease course. Preclinical and clinical analyses have elucidated changes in the mucosal layer of the duodenum potentially caused by dietary excess and obesity, which seem to be prevalent among individuals with metabolic disease. Supporting these findings, gastric bypass, a surgical procedure which removes the duodenum from the intestinal nutrient flow, has remarkable effects that improve, and often cause remission of, diabetes. From this perspective, we explore the rationale for targeting the duodenum with duodenal mucosal resurfacing (DMR). We examine the underlying physiology of the duodenum and its emerging role in T2DM pathogenesis, the rationale for targeting the duodenum by DMR as a potential treatment for T2DM, and current data surrounding DMR. Importantly, DMR has been demonstrated to change mucosal abnormalities common in those with obesity and diabetes. Given the multifactorial aetiology of T2DM, understanding proximate contributors to disease pathogenesis opens the door to rethinking therapeutic approaches to T2DM, from symptom management toward disease modification.

Reflux Symptoms Increase Following Sleeve Gastrectomy Despite Triage of Symptomatic Patients to Roux-en-Y Gastric Bypass.

BACKGROUND AND AIMS: Bariatric surgical options in obese patients include sleeve gastrectomy (SG) and roux-en-Y gastric bypass (RYGB), which may not be equivalent in risk of postoperative reflux symptoms. We evaluated risk and predictive factors for postbariatric surgery reflux symptoms. METHODS: Patients with obesity evaluated for bariatric surgery over a 15-month period were prospectively followed with validated symptom questionnaires (GERDQ, dominant symptom index: product of symptom frequency and intensity from 5-point Likert scores) administered before and after SG and RYGB. Esophageal testing included high-resolution manometry in all patients, and ambulatory reflux monitoring off therapy in those with abnormal GERDQ or prior reflux history. Univariate comparisons and multivariable analysis were performed to determine if preoperative factors predicted postoperative reflux symptoms. RESULTS: Sixty-four patients (median age 49.0 years, 84% female, median BMI 46.5 kg/m 2 ) fulfilled inclusion criteria and underwent follow-up assessment 4.4 years after bariatric surgery. Baseline GERDQ and dominant symptom index for heartburn were significantly higher in RYGB patients ( P ≤0.04). Despite this, median GERDQ increased by 2 (0.0 to 4.8) following SG and decreased by 0.5 (-1.0 to 5.0) following RYGB ( P =0.02). GERDQ became abnormal in 43.8% after SG and 18.8% after RYGB ( P =0.058); abnormal GERDQ improved in 12.5% and 37.5%, respectively ( P =0.041). In a model that included age, gender, BMI, acid exposure time, and type of surgery, multivariable analysis identified SG as an independent predictor of postoperative heartburn (odds ratio 16.61, P =0.024). CONCLUSIONS: Despite preferential RYGB when preoperative GERD was identified, SG independently predicted worsening heartburn symptoms after bariatric surgery.