Surgery-induced Weight Loss Research Articles

Effects of bariatric surgery on hyperuricemia and gout: a systematic review of the literature.

Gout is the most common form of inflammatory arthritis, and it is due to the deposition of monosodium urate crystals in the articular and extra-articular tissues. Body mass index is strongly correlated with elevated serum uric acid levels and gout is often associated with obesity and metabolic syndrome. Recommended nonpharmacological treatments for hyperuricemia and gout include dietary modifications and weight loss. Many studies have demonstrated that weight loss could reduce serum urate in patients with obesity and it is a commonly recommended treatment for gout. Bariatric surgery-induced weight loss exerts beneficial effects on hyperuricemia and gout, even if a possible raise of gout flares can be observed in patients with hyperuricemia early after surgery. The aim of this review is to systematically analyze all the studies published so far reporting a link between hyperuricemia and/or gout and bariatric surgery to obtain reliable figures on the incidence of this disease and describe the mechanisms underlying this association. Eleven studies accounting for 11,256 patients were included in the review. Mean preoperative prevalence of gout was 4.1%, while the preoperative prevalence of hyperuricemia ranged from 30.6% to 58%. After a mean follow-up of 8.5months, postoperative prevalence of gout significantly decreased to 2.9% (p < .007). The incidence of gout flares after bariatric surgery was higher in the early postoperative phase and progressively decreased over time. Similarly, serum uric acid concentrations showed an increase within the first postoperative month, which was followed by a progressive decrease below the preoperative value.

Energy expenditure, metabolic adaptation, physical activity and energy intake following weight loss: comparison between bariatric surgery and low-calorie diet.

Bariatric surgery remains the most effective treatment to achieve substantial weight loss; however, total daily energy expenditure and physical activity changes in response to such interventions have been seldom explored. In this prospective observational study, total daily energy expenditure (TDEE) using doubly labeled water and physical activity (SenseWear armband) was assessed in 17 females (mean ± SD: 48.6 ± 9.7 kg/m2, 43 ± 12 years) at baseline and 8 and 52 weeks following either bariatric surgery (BSG, N = 9) or a low-calorie diet (LCD, N = 8). Energy intake was assessed using the intake-balance method. After 8 weeks, weight loss was 16.0 ± 3.5 kg and TDEE decreased by 552 ± 319 kcal/d in BSG (P < 0.001) compared to 8.8 ± 3.4 kg and 256 ± 239 kcal/d in LCD (P < 0.05). After 52 weeks, weight loss was 44.3 ± 16.4 kg and TDEE decreased by 583 ± 418 kcal/d (P < 0.001), compared to 4.3 ± 6.7 kg and 84 ± 285 kcal/d in LCD (P > 0.05). TDEE was lower than predicted in BSG at 8 (P = 0.03) but not 52 weeks (P = 0.77). There was no evidence of metabolic adaptation in LCD. Average daily energy intake in BSG was 1403 ± 245 kcal/d compared to 2545 ± 398 kcal/d in LCD (P < 0.001). In BSG, step count and physical activity minutes were increased at 52 weeks compared to baseline (P = 0.03), whereas no significant changes were observed in LCD. Bariatric surgery-induced weight loss decreased TDEE at 8 weeks and 1 year, resulting in metabolic adaptation after 8 weeks that was reversed at 1 year. These changes were accompanied by an increase in physical activity.

Impact of Weight Loss on Olfaction in Patients Undergoing Bariatric Surgery.

Olfaction plays a vital role in regulating nutrition, avoiding potentially dangerous situations, and modulating behavior along with interpersonal relationships. Many common disorders can have a negative impact on olfaction; one of these is obesity. Bariatric surgery induces weight loss, and current evidence suggests that it can cause improvement in olfaction. However, more information is needed regarding this topic. One hundred eighty-five patients who underwent bariatric surgery and 184 age- and gender-matched control group who did not undergo any surgery have completed a questionnaire including items from the validated Self-Reported Mini Olfactory Questionnaire. Final analysis was based on 369 patients. There was a statistically significant difference between patients before and after surgery (p < 0.05). However, there was a statistically significant difference between people who underwent surgery with < 50% excess body weight loss and the control group but none with those > 50% excess body weight loss. No significant differences were found when comparing people with and without chronic illnesses, head and neck surgery, anti-allergy drug use, and COVID-19. Before surgery, there were statistically significant differences between patients with allergic rhinitis and polyps and those without, but no significant differences were observed after surgery. Patients had significantly improved olfactory scores post-surgery compared to before surgery. Patients who had > 50% excess body weight loss after surgery showed olfactory function as good as the general population represented by the control group. However, those with < 50% excess body weight loss had significantly worse olfactory scores compared to the general population.

Relationship between systemic biomarker of lipid peroxidation 4-hydroxynonenal and lipidomic profile of morbidly obese patients undergoing bariatric surgery

Obesity is characterized by fat accumulation, impaired metabolism and oxidative stress, frequently associated with lipid peroxidation and generation of bioactive 4-hydroxynonenal (4-HNE). This study aimed to evaluate the impact of bariatric surgery-induced weight loss on lipid peroxidation and associated perturbations in lipid profile. Plasma samples of twenty obese individuals before and 6 months after bariatric surgery were collected in addition to samples of ten healthy controls. HILIC-LC-MS/MS platform was used to characterize phospholipid profile, while lipid peroxidation markers 15-F2t-IsoP, 10-F4t-NeuroP and reactive aldehyde 4-HNE were quantified by RP-LC-MS/MS and GC-MS, respectively. Six months post-surgery lipid peroxidation markers decreased significantly and the BMI of morbidly obese patients decreased by 13 on average. Lipidomics analysis, identified 117 phospholipid species from seven classes, and showed obesity-associated lipidome perturbations, particularly in ether-linked phosphatidylethanolamines (PEo). A total of 45 lipid species were found to be significantly altered with obesity, while 10 lipid species correlated with lipid peroxidation markers. Sample pairwise analyses indicated an interesting link between 4-HNE and the amount of two PEos, PEo (38:2) and PEo (36:2). The results indicate that weight loss-induced improvement of redox homeostasis together with changes in lipid metabolites may serve as markers of metabolic improvement. However, further studies are needed to understand the role of obesity-induced oxidative stress on ether lipid biosynthesis and lipidome perturbations, as well as the impact of bariatric surgery on metabolic improvement.

The dual nature of DNA damage response in obesity and bariatric surgery-induced weight loss

This novel study applies targeted functional proteomics to examine tissues and cells obtained from a cohort of individuals with severe obesity who underwent bariatric surgery (BS), using a Reverse-Phase Protein Array (RPPA). In obese individuals, visceral adipose tissue (VAT), but not subcutaneous adipose tissue (SAT), shows activation of DNA damage response (DDR) markers including ATM, ATR, histone H2AX, KAP1, Chk1, and Chk2, alongside senescence markers p16 and p21. Additionally, stress-responsive metabolic markers, such as survivin, mTOR, and PFKFB3, are specifically elevated in VAT, suggesting both cellular stress and metabolic dysregulation. Conversely, peripheral blood mononuclear cells (PBMCs), while exhibiting elevated mTOR and JNK levels, did not present significant changes in DDR or senescence markers. Following BS, unexpected increases in phosphorylated ATM, ATR, and KAP1 levels, but not in Chk1 and Chk2 nor in senescence markers, were observed. This was accompanied by heightened levels of survivin and mTOR, along with improvement in markers of mitochondrial quality and health. This suggests that, following BS, pro-survival pathways involved in cellular adaptation to various stressors and metabolic alterations are activated in circulating PBMCs. Moreover, our findings demonstrate that the DDR has a dual nature. In the case of VAT from individuals with obesity, chronic DDR proves to be harmful, as it is associated with senescence and chronic inflammation. Conversely, after BS, the activation of DDR proteins in PBMCs is associated with a beneficial survival response. This response is characterized by metabolic redesign and improved mitochondrial biogenesis and functionality. This study reveals physiological changes associated with obesity and BS that may aid theragnostic approaches.

Gut-muscle communication links FGF19 levels to the loss of lean muscle mass following rapid weight loss

ObjectiveOptimal weight loss involves decreasing adipose tissue while preserving lean muscle mass. Identifying molecular mediators that preserve lean muscle mass is therefore a clinically important goal. We have shown that circulating, postprandial FGF19 levels are lower in patients with obesity and decrease further with comorbidities such as type 2 diabetes and MASLD. Preclinical studies have shown that FGF15 (mouse ortholog of human FGF19) is necessary to protect against lean muscle mass loss following metabolic surgery-induced weight loss in a mouse model of diet-induced obesity. We evaluated if non-surgical weight loss interventions also lead to increased systemic levels of FGF19 and whether FGF19 levels are predictive of lean muscle mass following rapid weight loss in human subjects with obesity. Research design and methodsWeight loss was induced in 176 subjects with obesity via a very low-energy diet, VLED (800 kcal/d) in the form of total liquid meal replacement for 3-4 months. We measured plasma FGF19 levels at baseline and following VLED-induced weight loss. Multiple linear regression was performed to assess if FGF19 levels were predictive of lean mass at baseline (obesity) and following VLED. ResultsPostprandial levels of FGF19 increased significantly following VLED-weight loss. Multiple linear regression analysis showed that baseline (obesity) FGF19 levels, but not post VLED FGF19 levels, significantly predicted the percent of lean muscle mass after VLED-induced weight loss, while controlling for age, sex, and the baseline percent lean mass. ConclusionThese data identify gut-muscle communication and FGF19 as a potentially important mediator of the preservation of lean muscle mass during rapid weight loss.

Effect of bariatric surgery in the body burden of persistent and non-persistent pollutants: longitudinal study in a cohort of morbidly obese patients.

Obesity is a pathological state that involves the dysregulation of different metabolic pathways and adipose tissue cells, constituting a risk factor for the development of other diseases. Bariatric surgery is the most effective treatment. The study of the behavior of pollutants in situations of extreme weight loss can provide biomonitoring information and tools to manage diseases of environmental etiology. To determine the prevalence of serum persistent and non-persistent pollutants in obese patients subjected to bariatric surgery and analyze the impact of sociodemographic variables on these changes. GC-MS/MS and UHPLC-MS/MS were utilized to determine the detection rates and concentrations of 353 compounds, including persistent organic pollutants (POPs), pesticides, pharmaceuticals, and rodenticide, in serum samples of 59 obese patients before and after undergoing bariatric surgery. Detection rates of p,p'-DDE, HCB, β-HCH, naphthalene, phenanthrene and PCB congeners 138, 153 and 180 significantly increased due to surgery-induced weight loss. Serum levels of p,p'-DDE, PCB-138, PCB-153 and PCB-180 also increased after surgery. Correlations between naphthalene levels, weight loss, variation of total lipids and time after surgery were found. Additionally, correlations were observed between concentrations of PCB-138 and weight loss, and between phenanthrene levels and reduction of total lipids. No statistically significant differences were observed for other groups of contaminants, pharmaceuticals and other chemicals included in the quantification methods. Increment of POPs was observed after bariatric surgery. Serum concentrations of POPs after surgery were influenced by adiposity-related variables. Although biomonitoring studies show a decreasing tendency of exposure, rapid weight loss leads to an increase of circulating POPs. Further research on the interplay between adipose tissue, POPs and peripheral organs is required.

Different effects of bariatric surgery on epigenetic plasticity in skeletal muscle of individuals with and without type 2 diabetes

AimBariatric surgery is highly effective for the treatment of obesity in individuals without (OB11OB: individuals with obesity.) and in those with type 2 diabetes (T2D22T2D: individuals with obesity and type 2 diabetes.). However, whether bariatric surgery triggers similar or distinct molecular changes in OB and T2D remains unknown. Given that individuals with type 2 diabetes often exhibit more severe metabolic deterioration, we hypothesized that bariatric surgery induces distinct molecular adaptations in skeletal muscle, the major site of glucose uptake, of OB and T2D after surgery-induced weight loss. MethodsAll participants (OB, n = 13; T2D, n = 13) underwent detailed anthropometry before and one year after the surgery. Skeletal muscle biopsies were isolated at both time points and subjected to transcriptome and methylome analyses using a comprehensive bioinformatic pipeline. ResultsBefore surgery, T2D had higher fasting glucose and insulin levels but lower whole-body insulin sensitivity, only glycemia remained higher in T2D than in OB after surgery. Surgery-mediated weight loss affected different subsets of genes with 2,013 differentially expressed in OB and 959 in T2D. In OB differentially expressed genes were involved in insulin, PPAR signaling and oxidative phosphorylation pathways, whereas ribosome and splicesome in T2D. LASSO regression analysis revealed distinct candidate genes correlated with improvement of phenotypic traits in OB and T2D. Compared to OB, DNA methylation was less affected in T2D in response to bariatric surgery. This may be due to increased global hydroxymethylation accompanied by decreased expression of one of the type 2 diabetes risk gene, TET2, encoding a demethylation enzyme in T2D. ConclusionOB and T2D exhibit differential skeletal muscle transcriptome responses to bariatric surgery, presumably resulting from perturbed epigenetic flexibility.

O-256 Evaluation of Anti-Mullerian hormone levels in reproductive age severely obese women six months after bariatric surgery

Abstract Study question Do serum levels of anti-Müllerian hormone (AMH) change in women of reproductive age following weight loss induced by bariatric surgery? Summary answer Following six months post-bariatric surgery, despite substantial weight loss, both Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy patients exhibited consistent AMH levels. What is known already Obesity negatively affects fertility, IVF outcomes, and potentially AMH) levels. AMH correlates to the number of growing follicles and is currently the best measure of ovarian reserve. Bariatric surgery (BS) has been considered as the most effective method to achieve sustainable weight loss. Many studies have demonstrated that there is an increase of spontaneous pregnancies and a reduction in complications during pregnancy or delivery post-bariatric surgery. Despite these benefits, the specific impact of BS on ovarian reserve and AMH levels remains unclear. Several studies have already considered the effects of surgery-induced weight loss on ovarian reserve, often showing conflicting results. Study design, size, duration This prospective study included 22 obese women in reproductive age with BMI ≥ 40 or ≥ 35 kg/m2 with at least one obesity-related comorbidity at baseline and 6 months after undergoing either sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB). Participants/materials, setting, methods Women aged 20–34 years with a median BMI of 41.53 kg/m² were included at baseline. Two medical consultations occurred: one preoperatively and another 6 months postoperatively. Each session included body weight and height measurements, as well as serum AMH testing using the Elecsys® AMH kit (Diagnostics Roche) and the electrochemiluminescence method - Cobas (Diagnostics Roche). Patients were divided into two groups: group 1 underwent RYGB, while group 2 underwent sleeve gastrectomy. Main results and the role of chance After six months post-bariatric surgery, all participants exhibited a significant reduction in BMI, with the median dropping from 41.53 kg/m² to 29.56 kg/m², representing a substantial 28.82% decrease (p &amp;lt; 0.001). In Group 1, the median BMI decreased from 38.51 kg/m² to 29.27 kg/m², a statistically significant reduction of 27.30% (p = 0.003). Group 2 also saw a significant drop, from 42.53 kg/m² to 30.10 kg/m², reflecting a 29.23% reduction (p = 0.003). Contrastingly, no significant changes in AMH levels were noted six months post-bariatric surgery. The median AMH level slightly decreased from 3.02 ng/mL to 2.95 ng/mL, a non-significant 2.32% reduction (p = 0.783). In Group 1, the median AMH level increased insignificantly from 2.54 ng/mL to 2.92 ng/mL, a 14.96% rise (p = 0.424). In Group 2, there was a non-significant 6.88% decrease, from 3.20 ng/mL to 2.98 ng/mL (p = 0.722). Pre-surgery, 12 patients reported regular menstrual cycles, while 10 reported irregular cycles. After six months, a significant increase (p = 0.021) in patients with regular menstrual cycles was observed, with 19 reporting regular cycles, while only 3 continued to experience irregular cycles. Limitations, reasons for caution Several limitations of the study should be considered, including the small sample size and the relatively short six-month follow-up period. It would be valuable to compare the study participants with a control group of women who achieved weight loss through diet and exercise. Wider implications of the findings The convergence of BS and fertility is an area of significant interest and clinical impact. This study suggests that BS has no significant impact on AMH levels or ovarian reserve in short-term. However, extending the study’s follow-up period would provide valuable insights into the long-term effects on ovarian reserve. Trial registration number not applicable

Tissue-specific inflammation and insulin sensitivity in subjects with obesity

Obesity is associated with low-grade inflammation and insulin resistance (IR). The contribution of adipose tissue (AT) and hepatic inflammation to IR remains unclear. We conducted a study across three cohorts to investigate this relationship.The first cohort consists of six women with normal weight and twenty with obesity. In women with obesity, we found an upregulation of inflammatory markers in subcutaneous and visceral adipose tissue, isolated AT macrophages, and the liver, but no linear correlation with tissue-specific insulin sensitivity. In the second cohort, we studied 24 women with obesity in the upper vs lower insulin sensitivity quartile. We demonstrated that several omental and mesenteric AT inflammatory genes and T cell-related pathways are upregulated in IR, independent of BMI. The third cohort consists of 23 women and 18 men with obesity, studied before and one year after bariatric surgery. Weight loss following surgery was associated with downregulation of multiple immune pathways in subcutaneous AT and skeletal muscle, alongside notable metabolic improvements.Our results show that obesity is characterised by systemic and tissue-specific inflammation. Subjects with obesity and IR show a more pronounced inflammation phenotype, independent of BMI. Bariatric surgery-induced weight loss is associated with reduced inflammation and improved metabolic health.

Abstract 17000: Adipokines and Subclinical Myocardial Injury Following Bariatric Surgery

Background: Bariatric surgery results in marked weight loss and has many cardiometabolic benefits. Adipokines, proteins secreted by adipose tissue with diverse metabolic effects, are affected by bariatric surgery. Whether favorable changes in adipokines after bariatric surgery are associated with improvements in cardiac biomarkers is unknown. Methods: We studied 294 bariatric surgery patients and 294 controls matched on age, sex, BMI, and diabetes in the Geisinger Obesity Registry. We measured serum markers of subclinical cardiac injury (high-sensitivity cardiac troponin I [hs-cTnI]), cardiac fibrosis (galectin-3), and adipokines (adiponectin, leptin, resistin, visfatin) prior to surgery and 6-18 months post-surgery in bariatric surgery patients and at similar intervals in controls. We used linear regression to evaluate the associations of changes in log-transformed adipokines with changes in log-transformed hs-cTnI and galectin-3. Results: Participants (mean age 45; 83% female; 97% White; mean BMI 47 kg/m 2 ) undergoing bariatric surgery lost 38.5 kg and matched controls gained 0.4 kg on average. Leptin, resistin, visfatin, hs-cTnI and galectin-3 decreased while adiponectin increased in bariatric surgery participants. There were no significant changes in any biomarkers in control participants. Increasing adiponectin and decreasing leptin were associated with decreases in hs-cTnI, but these associations were attenuated by adjustment for weight loss ( Table ). Decreasing resistin was linked to decreasing hs-cTnI and galectin-3, and decreasing visfatin with decreasing galectin-3, independent of weight loss. Conclusion: Bariatric surgery induced weight loss results in favorable changes in adipokines, which are associated with reversal of subclinical myocardial injury, and to a lesser degree, with decreasing myocardial fibrosis. Associations for some adipokines were weight loss-dependent, while others were independent of weight loss.

Abstract 15895: Bariatric Surgery and Subclinical Myocardial Injury

Background: Obesity is linked with subclinical myocardial injury, even in those with metabolically healthy obesity (MHO). There is limited data on the impact of weight loss via bariatric surgery on myocardial injury, particularly at different levels of metabolic health. Methods: We prospectively evaluated 294 Geisinger Obesity Institute Registry participants undergoing bariatric surgery and 294 controls matched on age, sex, body mass index (BMI;± 5kg/m 2 ) and diabetes status. High-sensitivity cardiac troponin I (hs-cTnI) was measured pre-operatively and at 6-18 months post-operatively in bariatric surgery patients, and at similar intervals in controls. Using linear regression, we examined the association of bariatric surgery with change in log transformed hs-cTnI (ln-hs-cTnI), stratified by metabolic health status: MHO (metabolic syndrome absent), metabolically unhealthy obesity (MUO; metabolic syndrome present), and MUO with diabetes. We used logistic regression to characterize the association of weight change (modeled as a restricted cubic spline) with the OR of transitioning from detectable to undetectable hs-cTnI (limit of detection 1.2ng/L). Results: The mean age was 45 years with 83% female, 97% White, and mean BMI of 47 kg/m 2 . Baseline characteristics of bariatric surgery patients and controls were similar. Bariatric surgery was associated with significant reduction in ln-hs-cTnI compared with controls in each stratum of metabolic health (P for interaction = 0.63; Panel A). Bariatric surgery was associated with an OR of 9.02 (95% CI 3.52-23.10) for transitioning from detectable to undetectable hs-cTnI, with a dose response association between weight loss and higher odds of developing undetectable hs-cTnI (Panel B). Conclusion: Bariatric surgery induced weight loss mitigates subclinical myocardial injury in graded fashion and across metabolic health strata, which may reflect one mechanism for the cardioprotective benefits of weight loss.

A Comparative Analysis of Safety and Efficacy of Bariatric Surgery During the COVID-19 Pandemic and Pre-Pandemic Period: Insights from the Tehran Obesity Treatment Study.

The COVID-19 pandemic has raised global health concerns and posed challenges for postoperative follow-up care for patients undergoing bariatric surgery due to social distancing rules. This was a cohort study on patients with morbid obesity who underwent bariatric surgery and had been enrolled in Tehran Obesity Treatment Study. Patients who had surgery between March 2020 and March 2021 were classified as those undergoing the procedure amid the COVID-19 pandemic, while those who had surgery between March 2017 and March 2018 were categorized as the pre-pandemic group. The study included 982 patients in the pre-COVID-19 pandemic group and 602 patients in the COVID-19 pandemic group, with mean ages of 39.61 and 39.51 years, respectively. After adjusting for preoperative body mass index (BMI) and surgery type, the patients who underwent surgery during the COVID-19 pandemic demonstrated comparable results to the pre-COVID-19 group in terms of total weight loss %, excess weight loss %, BMI reduction, and fat mass reduction during the 12-month postoperative period. Additionally, the rate of complications with a grade≥III based on the Clavien-Dindo classification was significantly lower in patients who underwent surgery during the COVID-19 pandemic. Notably, there were no deaths reported in either group. Despite social isolation and unfavorable lifestyle modifications, bariatric surgery-induced weight loss after one year was the same in patients undergoing the procedure either before or after the implementation of social distancing measures. More research is needed to analyze the influence of the COVID-19 pandemic on the long-term outcomes of bariatric surgery.

Limited Bariatric Surgery-induced Weight Loss in Subjects With Type 2 Diabetes: Predictor Variables in Adipose Tissue.

The impact of type 2 diabetes mellitus (T2D) at baseline on limited weight loss (WL) after bariatric surgery (BS) remains controversial, and the potential underlying mechanisms incompletely understood. We aimed at gaining further insight on this relationship and identifying novel associations between adipose tissue (AT) parameters and short-term WL outcomes in subjects with or without T2D undergoing BS. Mid-term WL trajectories after BS have been evaluated in a cohort of 1659 subjects (cohort 1) with (n = 543) and without T2D (n = 1116). Paired subcutaneous and visceral AT samples were obtained from a cohort of 48 pairs of subjects with and without T2D matched for age, sex, BMI, and type of BS (cohort 2). Differences in AT parameters between groups were evaluated and potential associations with WL response explored. T2D was independently associated with a 5% lesser mid-term WL in cohort 1, while HbA1c, insulin treatment, and number of T2D medications prior to BS were only related to short-term WL outcomes. In cohort 2, a number of differentially expressed genes in AT were identified between groups, while fat cell size and fibrosis were comparable. Subcutaneous ATG7 expression was found as an independent predictor of limited WL 1 year after surgery (β: -12.21 ± 4.41, P = .008) and its addition to a clinical model significantly improved the amount of WL variability explained (R2 = 0.131 vs R2 = 0.248, F change P = .009). Our results highlight the importance of T2D as determinant of limited WL following BS and suggest that dysregulated macroautophagy in subcutaneous AT may contribute to this association.

Factors Associated With Cognitive Improvement After Bariatric Surgery Among Patients With Severe Obesity in the Netherlands

Bariatric surgery-induced weight loss is often associated with improved cognitive function. However, improvement in cognitive function is not always exhibited by all patients, and the mechanisms behind cognitive improvement remain unknown. To investigate the association of changes in adipokines, inflammatory factors, mood, and physical activity with alterations in cognitive function after bariatric surgery among patients with severe obesity. This cohort study included 156 patients with severe obesity (body mass index [calculated as weight in kilograms divided by height in meters squared], >35) eligible for Roux-en-Y gastric bypass, aged between 35 and 55 years, who were enrolled in the BARICO (Bariatric Surgery Rijnstate and Radboudumc Neuroimaging and Cognition in Obesity) study between September 1, 2018, and December 31, 2020. Follow-up was completed July 31, 2021; 146 participants completed the 6-month follow-up and were included in the analysis. Roux-en-Y gastric bypass. Overall cognitive performance (based on a 20% change index of the compound z score), inflammatory factors (eg, C-reactive protein and interleukin 6 levels), adipokines (eg, leptin and adiponectin levels), mood (assessed via the Beck Depression Inventory), and physical activity (assessed with the Baecke questionnaire). A total of 146 patients (mean [SD] age, 46.1 [5.7] years; 124 women [84.9%]) completed the 6-month follow-up and were included. After bariatric surgery, all plasma levels of inflammatory markers, including C-reactive protein (median change, -0.32 mg/dL [IQR, -0.57 to -0.16 mg/dL]; P < .001) and leptin (median change, -51.5 pg/mL [IQR, -68.0 to -38.4 pg/mL]; P < .001), were lower, whereas adiponectin levels were higher (median change, 0.15 μg/mL [IQR, -0.20 to 0.62 µg/mL]; P < .001), depressive symptoms were (partly) resolved (median change in Beck Depression Inventory score, -3 [IQR, -6 to 0]; P < .001), and physical activity level was higher (mean [SD] change in Baecke score, 0.7 [1.1]; P < .001). Cognitive improvement was observed in 43.8% (57 of 130) of the participants overall. This group had lower C-reactive protein (0.11 vs 0.24 mg/dL; P = .04) and leptin levels (11.8 vs 14.5 pg/mL; P = .04) and fewer depressive symptoms at 6 months (4 vs 5; P = .045) compared with the group of participants who did not show cognitive improvement. This study suggests that lower C-reactive protein and leptin levels, as well as fewer depressive symptoms, might partly explain the mechanisms behind cognitive improvement after bariatric surgery.

Individuals with type 2 diabetes have higher density of small intestinal neurotensin-expressing cells

Neurotensin (NT) is a gastro-intestinal hormone involved in several pathways that regulate energy and glucose homeostasis. NT was hypothesized to act in synergy with incretin hormones to potentiate its anti-diabetic effects. Additionally, circulating NT levels were shown to rise after bariatric surgery-induced weight loss. Knowledge of NT-secreting cells distribution along the small intestine and its variation according to diabetes status could provide insights on NT role in mediating type 2 diabetes (T2D) improvement after bariatric surgery. So, our aims were to characterize NT-expressing cell distribution along the human small intestine and to compare the relative density of NT-expressing cells in the small intestine of individuals with and without T2D undergoing bariatric surgery for obesity treatment. Autopsy-derived small intestine fragments (n = 30) were obtained at every 20 cm along the entire intestinal length. Additionally, jejunum biopsies (n = 29) were obtained during elective gastric bypass interventions from patients with (n = 10) or without T2D (n = 18). NT-expressing cells were identified by immunohistochemistry and quantified via computerized morphometric analysis. NT-expressing cell density increased along the human small intestine. NT-expressing cell density was significantly higher from 200 cm distal to the duodenojejunal flexure onward, as well as in subjects with T2D when compared to those without T2D. NT-expressing cell density increases along the human small gut, and a higher density is found in individuals with T2D. This finding suggests a potential role for NT in the mechanisms of disease and T2D improvement observed after bariatric surgery.

Abstract P117: Weight Loss is Associated With Increases in Mitochondrial DNA Copy Number

Background: Mitochondrial DNA copy number (mtDNA-CN) is a surrogate measure of mitochondrial function that is independently associated with increased cardiovascular disease risk. Individuals with obesity and cardiometabolic risk factors have lower mtDNA-CN levels. However, the modifiability of mtDNA-CN following a weight loss intervention has remained largely unexplored. Hypothesis: Bariatric surgery-induced weight loss is associated with longitudinal increases in circulating mtDNA-CN levels. Methods: In the BARI-Heart prospective cohort of bariatric surgery patients, we quantified mtDNA-CN from whole blood samples collected at three visits: 3 to 6 months prior to surgery, 2-4 weeks prior to surgery, and 6 months post-surgery. We used linear mixed models with random effects to assess changes in mtDNA-CN after bariatric surgery, with the pre-surgery visits while awaiting bariatric surgery serving as the control period. We used multivariable linear regression to evaluate the dose-response association between weight loss and change in mtDNA-CN. Results: We included 71 participants (mean age 45 years, 74% female, 88% White). While mtDNA-CN levels did not change significantly during the pre-surgery period (V1 to V2), mtDNA-CN significantly increased after bariatric surgery (V2 to V3) (Figure). In linear mixed models adjusting for age, sex, and smoking, mtDNA-CN was higher after bariatric surgery than immediately prior to bariatric surgery (Table: ß=0.141, p &lt; 0.001). This increase in mtDNA-CN remained significant following further adjustment for changes in cardiometabolic risk factors (ß=0.116, p &lt; 0.01). In linear regression, each 10% greater weight loss was associated with a 1.6% increase in mtDNA-CN. Conclusions: Weight loss via bariatric surgery is associated with significant increases in mtDNA-CN, independent of cardiometabolic risk factors. Improvements in mitochondrial function may mediate some of the cardiovascular benefits of significant weight loss.

Cognition and brain oxygen metabolism improves after bariatric surgery-induced weight loss: A pilot study.

The primary objectives of this pilot study were to assess cognition and cerebral metabolic rate of oxygen (CMRO2) consumption in people with severe obesity before (baseline), and again, 2- and 14-weeks after sleeve gastrectomy bariatric surgery. Six people with severe/class 3 obesity (52 ± 10 years, five females, body mass index (BMI) = 41.9 ± 3.9 kg/m2), and 10 normal weight sex- and age-matched healthy controls (HC) (48 ± 6 years, eight females, 22.8 ± 1.9 kg/m2). Global CMRO2 was measured non-invasively using MRI and cognition using the Integneuro testing battery. Following a sleeve gastrectomy induced weight loss of 6.4 ± 2.5kg (% total-body-weight-lost = 5.4) over two-weeks, cognition total scores improved by 0.8 ± 0.5 T-scores (p=0.03, 15.8% improvement from baseline). Weight loss over 14-weeks post-surgery was 15.4 ± 3.6kg (% total-body-weight-lost = 13.0%) and cognition improved by 1.1 ± 0.4 (p=0.003, 20.6% improvement from baseline). At 14-weeks, cognition was 6.4 ± 0.7, comparable to 6.0 ± 0.6 observed in the HC group. Baseline CMRO2 was significantly higher compared to the HC (230.4 ± 32.9 vs. 177.9 ± 33.9 µmol O2/100 g/min, p=0.02). Compared to baseline, CMRO2 was 234.3 ± 16.2 µmol O2/100 g/min at 2-weeks after surgery (p=0.8, 1.7% higher) and 217.3 ± 50.4 at 14-weeks (p=0.5, 5.7% lower) after surgery. 14-weeks following surgery, CMRO2 was similar to HC (p=0.17). Sleeve gastrectomy induced weight loss was associated with an increase in cognition and a decrease in CMRO2 observed 14-weeks after surgery. The association between weight loss, improved cognition and CMRO2 decrease should be evaluated in larger future studies.

Bariatric surgery-induced weight loss and associated genome-wide DNA-methylation alterations in obese individuals

BackgroundObesity is a multifactorial and chronic condition of growing universal concern. It has recently been reported that bariatric surgery is a more successful treatment for severe obesity than other noninvasive interventions, resulting in rapid significant weight loss and associated chronic disease remission. The identification of distinct epigenetic patterns in patients who are obese or have metabolic imbalances has suggested a potential role for epigenetic alterations in causal or mediating pathways in the development of obesity-related pathologies. Specific changes in the epigenome (DNA methylome), associated with metabolic disorders, can be detected in the blood. We investigated whether such epigenetic changes are reversible after weight loss using genome-wide DNA methylome analysis of blood samples from individuals with severe obesity (mean BMI ~ 45) undergoing bariatric surgery.ResultsOur analysis revealed 41 significant (Bonferroni p < 0.05) and 1169 (false discovery rate p < 0.05) suggestive differentially methylated positions (DMPs) associated with weight loss due to bariatric surgery. Among the 41 significant DMPs, 5 CpGs were replicated in an independent cohort of BMI-discordant monozygotic twins (the heavier twin underwent diet-induced weight loss). The effect sizes of these 5 CpGs were consistent across discovery and replication sets (p < 0.05). We also identified 192 differentially methylated regions (DMRs) among which SMAD6 and PFKFB3 genes were the top hypermethylated and hypomethylated regions, respectively. Pathway enrichment analysis of the DMR-associated genes showed that functional pathways related to immune function and type 1 diabetes were significant. Weight loss due to bariatric surgery also significantly decelerated epigenetic age 12 months after the intervention (mean = − 4.29; p = 0.02).ConclusionsWe identified weight loss-associated DNA-methylation alterations targeting immune and inflammatory gene pathways in blood samples from bariatric-surgery patients. The top hits were replicated in samples from an independent cohort of BMI-discordant monozygotic twins following a hypocaloric diet. Energy restriction and bariatric surgery thus share CpGs that may represent early indicators of response to the metabolic effects of weight loss. The analysis of bariatric surgery-associated DMRs suggests that epigenetic regulation of genes involved in endothelial and adipose tissue function is key in the pathophysiology of obesity.

The antigen CD300e drives T cell inflammation in adipose tissue and elicits an antibody response predictive of the insulin sensitivity recovery in obese patients

Obesity and insulin resistance (IR), the key features of metabolic syndrome, are closely associated with a state of chronic, low-grade inflammation. Bariatric surgery leads to a considerable reduction in the adipose tissue mass and systemic inflammation along with a reduction of IR, with a whole-body metabolic improvement. However, a sizable portion of people experience an IR relapse within few years of remission.Numerous studies have attempted to explore the best clinical predictors of the improvement of insulin sensitivity and the maintenance of glucose homeostasis after bariatric surgery, but no simple fasting blood test has been found to be effective in predicting the short and long-term beneficial effects on glycaemia.With the present study, we investigated T-cell and antibody responses against CD300e, an antigen highly expressed in the adipose tissue of patients with obesity before the bariatric surgery-induced weight loss. We found both in fat tissue and in peripheral blood anti-CD300e-specific T helper 1 responses. Moreover, we evidenced in the sera of individuals with obesity an antibody response towards CD300e and revealed the existence of a significant correlation between the level of antibodies before surgery and the maintenance of glucose control after the intervention.