Liraglutide for the Treatment of Weight Regain After Bariatric Surgery: A Systematic Review and Meta-analysis.

INTRODUCTION: The efficacy of liraglutide for treating type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains unclear. METHODS: We searched PubMed, Embase, and Cochrane Library databases in January 2024. A random-effects model was employed to compute mean differences (MD) and events per 100 observations with 95% confidence intervals (CI) for continuous and binary endpoints. Statistical analysis was performed using R software. RESULTS: A total of 16 studies were included and 881 individuals. Patients were mostly female (50%), aged 36 to 55 years, with a mean body mass index (BMI) of 39.4 kg/m2, and had BS surgery 5 years prior. Over a mean follow-up time ranging from 3 months to 4 years, it was observed a statistically significant reduction in BMI (MD - 8.56 kg/m2; 95% CI 3.34 to 13.79; p < 0.01) and a mean reduction in total weight (MD - 16.03 kg; 95% CI 0.03 to 32.02; p = 0.05) after liraglutide use. Additionally, 65% of patients undertaking liraglutide showed total body weight loss (BWL) above 5% (65.8 events per 100 observations; 95% CI 54.96 to 75.20; p < 0.01), while 26% lost more than 10% of total BWL (26.77 events per 100 observations; 95% CI 19.17 to 36.02; p < 0.01). A limitation is a variability between the studies. CONCLUSIONS: Our findings support the use of liraglutide for weight management in patients who experience weight regain after BS. Liraglutide is well tolerated and promotes significant weight loss, providing clinicians with a therapeutic option for this clinical challenge.

The impact of the obesity onset on the inflammatory and glycemic profile of women with severe obesity.

BACKGROUND: The stage of life at the onset of obesity is an important factor in assessing inflammatory state and cardiometabolic risk. OBJECTIVES: This study aimed to evaluate the relationship between the obesity onset and the inflammatory profile in women with severe obesity. SETTING: Public hospital, Brazil. METHODS: Forty-eight women with severe obesity (20-59 yr old) were evaluated according to weight, height, neck circumference (NC), waist circumference (WC), and hip circumference, as well blood metabolic and inflammatory parameters. The participants were grouped according to obesity onset stage of life (early group: ≤19 yr; late group: >19 yr). RESULTS: The demographic means of the participants were: age of 39.7 years, weight of 122.7 kg and body mass index (BMI) of 48.4 kg/m2. The late group presented significantly higher values of leptin (lep)/adiponectin (adipo) ratio and homeostatic model assessment for insulin resistance (HOMA-IR) than the early group. The late group also had a lower adipo/lep ratio. Moreover, the late group showed correlations between the lep/adipo ratio and BMI (r = .460, P = .021), NC (r = .478, P = .016), and WC (r = .535, P = .006). Adipo was also correlated with NC (r = -.418, P = .038), WC (r = -.437, P = .029), and glycated hemoglobin (HbA1C) (r = -.485, P = .019). By contrast, in the early group, the lep/adipo ratio showed correlations with insulin (r = .647, P = .004) and HOMA-B (r = .564, P = .015). CONCLUSIONS: The inflammatory profile is correlated with anthropometric values in women with late-onset obesity. Inflammatory markers seemed to correlate with the glycemic profile in women with early-onset obesity. Furthermore, inflammation was higher in women with late-onset obesity compared to those with early-onset obesity.

HOMA-IR as a Predictor of PAI-1 Levels in Women with Severe Obesity.

BACKGROUND: Obesity is a chronic inflammatory disorder that increases the risk of cardiovascular diseases (CVDs). Given the high CVD mortality rate among individuals with obesity, early screening should be considered. Plasminogen activator inhibitor (PAI-1), a cytokine that links obesity and CVDs, represents a promising biomarker. However, PAI-1 is not part of the clinical routine due to its high cost. Therefore, it is necessary to find good predictors that would allow an indirect assessment of PAI-1. METHODS: This study enrolled 47 women with severe obesity (SO). The obtained anthropometric measurements included weight, height, neck (NC), waist (WC), and hip circumference (HC). Blood samples were collected to analyse glucose and lipid profiles, C-reactive protein, liver markers, adiponectin, and PAI-1 (determined by ELISA immunoassay). Homeostasis model assessment-adiponectin (HOMA-AD), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), triglyceride-glucose index (TyG), and atherogenic index of plasma (AIP) were calculated. The women were grouped according to PAI-1 levels. The data were analysed using IBM SPSS Statistics, version 21. The significance level for the analysis was set at 5%. RESULTS: Women with SO who have higher levels of PAI-1 have lower values of high-density lipoprotein cholesterol (HDL) (p = 0.037) and QUICKI (0.020) and higher values of HOMA-AD (0.046) and HOMA-IR (0.037). HOMA-IR was demonstrated to be a good predictor of PAI-1 in this sample (B = 0.2791; p = 0.017). CONCLUSIONS: HOMA-IR could be used as a predictor of PAI-1 levels, pointing out the relevance of assessing glycaemic parameters for the prevention of CVDs in women with SO.

Genetic variants in DBC1, SIRT1, UCP2 and ADRB2 as potential biomarkers for severe obesity and metabolic complications.

Introduction: Obesity is a multifactorial disease associated with the development of many comorbidities. This disease is associated with several metabolic alterations; however, it has been shown that some individuals with obesity do not exhibit metabolic syndrome. Adipose tissue neutralizes the detrimental effects of circulating fatty acids, ectopic deposition, and inflammation, among others, through its esterification into neutral lipids that are stored in the adipocyte. However, when the adipocyte is overloaded, i.e., its expansion capacity is exceeded, this protection is lost, resulting in fatty acid toxicity with ectopic fat accumulation in peripheral tissues and inflammation. In this line, this study aimed to investigate whether polymorphisms in genes that control adipose tissue fat storage capacity are potential biomarkers for severe obesity susceptibility and also metabolic complications. Methods: This study enrolled 305 individuals with severe obesity (cases, BMI≥35 kg/m2) and 196 individuals with normal weight (controls, 18.5≤BMI≤24.9 kg/m2). Demographic, anthropometric, biochemical, and blood pressure variables were collected from the participants. Plasma levels of leptin, resistin, MCP1, and PAI1 were measured by Bio-Plex 200 Multiplexing Analyzer System. Genomic DNA was extracted and variants in DBC1 (rs17060940), SIRT1 (rs7895833 and rs1467568), UCP2 (rs660339), PPARG (rs1801282) and ADRB2 (rs1042713 and rs1042714) genes were genotyped by PCR allelic discrimination using TaqMan® assays. Results: Our findings indicated that SIRT1 rs7895833 polymorphism was a risk factor for severe obesity development in the overdominant model. SIRT1 rs1467568 and UCP2 rs660339 were associated with anthropometric traits. SIRT1 rs1467568 G allele was related to lower medians of body adipose index and hip circumference, while the UCP2 rs660339 AA genotype was associate with increased body mass index. Additionally, DBC1 rs17060940 influenced glycated hemoglobin. Regarding metabolic alterations, 27% of individuals with obesity presented balanced metabolic status in our cohort. Furthermore, SIRT1 rs1467568 AG genotype increased 2.5 times the risk of developing metabolic alterations. No statistically significant results were observed with Peroxisome Proliferator-Activated Receptor Gama and ADRB2 polymorphisms. Discussion/Conclusion: This study revealed that SIRT1 rs7895833 and rs1467568 are potential biomarkers for severe obesity susceptibility and the development of unbalanced metabolic status in obesity, respectively. UCP2 rs660339 and DBC1 rs17060940 also showed a significant role in obesity related-traits.

Long-term (11 Years) Results of Laparoscopic Gastric Bypass: Changes in Weight, Blood Levels of Sugar and Lipids, and Late Adverse Effects : Laparoscopic Gastric Bypass Results.

PURPOSE: Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) remains the most effective procedure to treat severe obesity with proven short- and intermediate-term benefits. The main goal is to describe the effects on weight and biochemical laboratory tests after long-term follow-up (11 years). MATERIALS AND METHODS: A prospective cohort of adults with obesity treated with LRYGB between 2004 and 2010 in one center were studied. Patients with prior bariatric or upper digestive tract surgery, hiatal hernia >4 cm, alcoholism, or decompensated conditions were excluded. The study enrolled 123 patients, with a mean follow-up of 133±29 months and a 14% loss of participants. RESULTS: The percentage of Total Weight Loss (%TWL) at one, five, and eleven years was 30.3±8.4%, 29.1±6.9%, and 23.4±7%, respectively. Of the patients, 61.3% (65/106) maintained a %TWL≥20 after eleven years. Recurrent Weight Gain (RWG) at five and eleven years was 2.6±11.4% and 11 ±11.5%, respectively. At the end of the follow-up, 31.1% (33/106) of patients had RWG≥15%. Hypercholesterolemia and hypertriglyceridemia improved in 85.7% (54/63) and 90.2% (7/61) of the cohort, respectively. Remission of diabetes occurred in 80% of this subgroup. Gallstones developed in 28% of patients, and bowel obstruction due to internal hernia occurred in 9.4%. Anemia due to iron deficiency appeared in 25 patients. CONCLUSION: After surgery, there is a significant and durable loss of weight, with a tendency for late Recurrent Weight Gain. Furthermore, the improvement in biochemical parameters is sustained over time, but surgery's adverse effects may appear later.

Liraglutide effectiveness in preoperative weight-loss for patients with severe obesity undergoing bariatric-metabolic surgery.

Preoperative management of patients living with severe obesity can be challenging; in this context, the preoperative weight loss may help to obtain better outcomes and less morbidity for bariatric surgery. Therefore, we evaluated the effectiveness of GLP-1 analogue Liraglutide in preoperative weight loss. We performed a single-center, quasi-experimental prospective study. Eligible participants were adults in preoperative management for bariatric-metabolic surgery with body-mass index ≥ 48 kg/m2. All patients were assigned liraglutide treatment, with an initial dose of 0.6 mg subcutaneous per day, the dose was increased each week until reaching 3.0 mg for 12 weeks. Weight loss and body composition were evaluated monthly using bioelectric impedance (BIA) (InBody 770 Scale®). We analyzed data using descriptive statistics, central tendency measures and dispersion for quantitative variables and absolute and relative frequencies for qualitative variables. A total of 37 individuals were included in this study, 28 (76%) were female and 9 (24%) were males, with an average age of 44 years. About the BMI, 19 patients (51%) had a BMI > 50 kg/m2, 10 (27%) > 40 kg/m2 and 8 (22%) > 60 kg/m2; with a total average BMI of 56.04 kg/m2. The initial weight was 147.4 ± 14.9 kg which decreased to 139.3 ± 16.8 kg; after 3 months of liraglutide administration. A total of 35 patients had some degree of weight loss (94.6%), while 2 (5.40%) had no weight changes. The total weight loss was 5.50% at 3 months of liraglutide treatment. Liraglutide could be an effective adjuvant therapy for preoperative weight loss in patients living with severe obesity.

Adequacy of basal metabolic rate prediction equations in individuals with severe obesity: A systematic review and meta-analysis.

The determination of energy requirements in clinical practice is based on basal metabolic rate (BMR), frequently predicted by equations that may not be suitable for individuals with severe obesity. This systematic review and meta-analysis examined the accuracy and precision of BMR prediction equations in adults with severe obesity. Four databases were searched in March 2021 and updated in May 2023. Eligible studies compared BMR prediction equations with BMR measured by indirect calorimetry. Forty studies (age: 28-55 years, BMI: 40.0-62.4 kg/m2) were included, most of them with a high risk of bias. Studies reporting bias (difference between estimated and measured BMR) were included in the meta-analysis (n = 20). Six equations were meta-analyzed: Harris & Benedict (1919); WHO (weight) (1985); Owen (1986); Mifflin (1990); Bernstein (1983); and Cunningham (1980). The most accurate and precise equations in the overall analysis were WHO (-12.44 kcal/d; 95%CI: -81.4; 56.5 kcal/d) and Harris & Benedict (-18.9 kcal/d; 95%CI -73.2; 35.2 kcal/d). All the other equations tended to underestimate BMR. Harris & Benedict and WHO were the equations with higher accuracy and precision in predicting BMR in individuals with severe obesity. Additional analyses suggested that equations may perform differently according to obesity BMI ranges, which warrants further investigation.

Metabolic and Bariatric Surgery in Patients with Obesity Class V (BMI > 60 kg/m2): a Modified Delphi Study.

BACKGROUND: Metabolic and bariatric surgery (MBS) is the preferred method to achieve significant weight loss in patients with Obesity Class V (BMI > 60 kg/m2). However, there is no consensus regarding the best procedure(s) for this population. Additionally, these patients will likely have a higher risk of complications and mortality. The aim of this study was to achieve a consensus among a global panel of expert bariatric surgeons using a modified Delphi methodology. METHODS: A total of 36 recognized opinion-makers and highly experienced metabolic and bariatric surgeons participated in the present Delphi consensus. 81 statements on preoperative management, selection of the procedure, perioperative management, weight loss parameters, follow-up, and metabolic outcomes were voted on in two rounds. A consensus was considered reached when an agreement of ≥ 70% of experts' votes was achieved. RESULTS: A total of 54 out of 81 statements reached consensus. Remarkably, more than 90% of the experts agreed that patients should be notified of the greater risk of complications, the possibility of modifications to the surgical procedure, and the early start of chemical thromboprophylaxis. Regarding the choice of the procedure, SADI-S, RYGB, and OAGB were the top 3 preferred operations. However, no consensus was reached on the limb length in these operations. CONCLUSION: This study represents the first attempt to reach consensus on the choice of procedures as well as perioperative management in patients with obesity class V. Although overall consensus was reached in different areas, more research is needed to better serve this high-risk population.

Muscle Quality Index in Morbidly Obesity Patients Related to Metabolic Syndrome Markers and Cardiorespiratory Fitness.

BACKGROUND: Muscle quality index (MQI) is an emerging health indicator obtained by dividing handgrip strength by body mass index (BMI) that needs to be studied in morbidly obese patients (defined by BMI ≥ 35 kg/m2). OBJECTIVE: To determine the association between MQI, metabolic syndrome (MetS) markers, and cardiorespiratory fitness (CRF), and as a second objective to determine the potential mediation role of MQI in the relationship between abdominal obesity and systolic blood pressure (SBP) in this sample. METHODS: This cross-sectional study included 86 severely/morbidly obese patients (age = 41.1 ± 11.9 y, nine men). MQI, metabolic syndrome markers, CRF, and anthropometric parameters were measured. Two groups were developed according to MQI; High-MQI (n = 41) and Low-MQI (n = 45). RESULTS: The Low-MQI group reported higher abdominal obesity (High-MQI: 0.7 ± 0.1 vs. Low-MQI: 0.8 ± 0.1 WC/height; p = 0.011), SBP (High-MQI: 133.0 ± 17.5 vs. Low-MQI: 140.1 ± 15.1 mmHg; p = 0.048), and lower CRF (High-MQI; 26.3 ± 5.9 vs. Low-MQI; 22.4 ± 6.1 mL/kg/min, p = 0.003) than the High-MQI group. Waist-to-height ratio (ß: -0.07, p = 0.011), SBP (ß: -18.47, p = 0.001), and CRF (ß: 5.21, p = 0.011) were linked to MQI. In a mediation model, the indirect effect confirms that MQI is a partial mediator of the association between abdominal obesity with SBP. CONCLUSIONS: MQI in morbidly obesity patients reported an inverse association with MetS markers and a positive association with CRF (VO2max). It mediates the relationship between abdominal obesity and SBP.

Equations based on body mass index for body composition estimations of women presenting grade III obesity / Ecuaciones a partir del índice de masa corporal para estimar la composición corporal de mujeres con obesidad III

ABSTRACT Objective To develop and validate predictive equations to estimate the body composition of women with grade III obesity, using the body mass index (BMI) as a predictive variable. Methods This cross-sectional study involved 104 patients treated at the hospital of the Universidade Federal do Rio de Janeiro randomly divided into two groups, the Equation Group, used to generate regression equations, and the Validation Group, used to validate the equations. Body fat mass (BFM), body fat percentage (BFP), skeletal muscle mass (SMM), fat-free mass (FFM) and total body water content (TBW) were valuated employing the bioimpedance method (InBody® 230). Results Polynomial equations exhibited the best fit and a general trend of results normalized by height squared presenting higher coefficients of determination (r2) was noted, positively affecting equation validations. Only one exception was observed, since the body fat percentage index (BFPI) resulted in an even lower correlation with BMI. Only these variables exhibited low r2 (0.11 to 0.29), while r2 values ranged from 0.51 to 0.94 for the other results. Conclusion Except for the BFP and BFPI, body composition can be estimated by the application of predictive BMI-based models. The equations employed for the indices normalized by the square of height were better predictors, while the use of equations that do not employ this normalization should consider the caveat that individuals with extreme BMI values (40 to 76 kg/m2) present greater estimate deviations in relation to the measured values.

RESUMEN Objetivo Desarrollar y validar ecuaciones predictivas para estimar la composición corporal de mujeres con obesidad III, utilizando el índice de masa corporal (IMC) como variable predictiva. Métodos Este estudio transversal involucró a 104 pacientes atendidos por el Hospital Universitario de la Universidad Federal de Río de Janeiro, divididos aleatoriamente en dos grupos. La masa de grasa corporal (MGC), el porcentaje de grasa corporal (PGC), la masa musculoesquelética (MME), la masa libre de grasa (MLG) y el contenido de agua total (ACT) fueron valorados por el método de bioimpedancia (InBody® 230). Resultados Las ecuaciones polinómicas presentaron un mejor ajuste y se observó una tendencia general de resultados normalizados, con mayores coeficientes de determinación (r2), lo cual afectó positivamente las validaciones de las ecuaciones. Se observó apenas una excepción, en relación con el PGC, pues el índice de porcentaje de grasa corporal (IPGC) tuvo una correlación menor con el IMC. Estas variables exhibieron un r2 bajo (0,11 a 0,29). Los valores de r2 oscilaron entre 0,51 y 0,94 para los demás resultados. Conclusión Con excepción del PGC y el IPGC, la composición corporal puede estimarse por medio de la aplicación de modelos predictivos basados en el IMC. Las ecuaciones empleadas por los índices normalizados por el cuadrado de la estatura fueron mejores predictores, en tanto que el uso de las ecuaciones que no emplean esa normalización debe considerar la advertencia de que individuos con valores extremos de IMC (40 a 76 kg/m2) presentan una mayor estimación de las desviaciones en relación con los valores medidos.

Effects of Roux-en-Y gastric bypass on the metabolic profile and systemic inflammatory status of women with metabolic syndrome: randomized controlled clinical trial.

BACKGROUND: Obesity remains a public health problem worldwide. The high prevalence of this condition in the population raises further concerns, considering that comorbidities are often associated with obesity. Among the comorbidities closely associated with obesity, metabolic syndrome (MS) is particularly important, which potentially increases the risk of manifestation of other disorders, such as the prothrombotic and systemic pro-inflammatory states. METHODS: A randomized, controlled clinical trial was performed involving female patients (n = 32) aged between 18 and 65 years, with a clinical diagnosis of MS, with severe obesity undergoing Roux-en-Y gastric bypass (RYGB). The study design followed the Consolidated Standards of Reporting Trials statement (CONSORT). Lipid profile, blood glucose and adipokines (adiponectin, leptin, and resistin) and (cytokines IL-1ß, IL-6, IL-17, IL-23, and TNF-α) in blood plasma samples were evaluated before and six months after RYGB. RESULTS: Patients undergoing RYGB (BSG) showed a significant improvement from preoperative grade III obesity to postoperative grade I obesity. The results showed that while HDL levels increased, the other parameters showed a significant reduction in their postoperative values when compared not only to the values observed before surgery in the BSG group, but also to the values obtained in the control group (CG). As for systemic inflammatory markers adiponectin, leptin, resistin, IL-1ß, IL-6, IL-17, IL-23 and TNF- α it was observed that the levels of resistin and IL-17 in the second evaluation increased significantly when compared to the levels observed in the first evaluation in the CG. In the BSG group, while the levels of adiponectin increased, the levels of the other markers showed significant reductions in the postoperative period, in relation to the respective preoperative levels. The analysis of Spearman's correlation coefficient showed a significant positive correlation between IL-17 and IL-23 in the preoperative period, significant positive correlations between TNF-α and IL-6, TNF-α and IL-17, IL-6 and IL-17, and IL-17 and IL-23 were observed postoperatively. CONCLUSIONS: According to our results, the reduction of anthropometric measurements induced by RYGB, significantly improves not only the plasma biochemical parameters (lipid profile and glycemia), but also the systemic inflammatory status of severely obese patients with MS. Trials registration NCT02409160.

Postoperative Resting Metabolic Rate and Successful Weight Loss After Roux-en-Y Gastric Bypass.

OBJECTIVE: To analyze whether changes in RMR 6 months after RYGB could be a predictor of weight loss on late follow-up. METHODS: Prospective study of 45 individuals submitted to RYGB in a university tertiary care hospital. Body composition was evaluated by bioelectrical impedance analysis and RMR by indirect calorimetry before (T0), 6 (T1), and 36 months (T2) after surgery. RESULTS: RMR/day was lower in T1 (1.552 ± 275 kcal/day) than in T0 (1734 ± 372 kcal/day; p < 0.001) with a return to similar values at T2 (1.795 ± 396 kcal/day; p < 0.001). In T0, there was no correlation between RMR/kg and body composition. In T1, there was a negative correlation between RMR and BW, BMI, and % FM, and a positive correlation with % FFM. The results in T2 were similar to T1. There was a significant increase in RMR/kg between T0, T1, and T2 (13.6 ± 2.2 kcal/kg, 16.9 ± 2.7 kcal/kg, and 19.9 ± 3.4 kcal/kg) in the total group and according to gender. Eighty percent of the patients who had increased RMR/kg ≥ 2 kcal at T1 achieved > 50% EWL in T2, particularly in women (odds ratio: 27.09, p < 0.037). CONCLUSIONS: The increase in RMR/kg after RYGB is a major factor related to a satisfactory % excess weight loss on late follow-up.

Acute effects of different intensities resistance training on inflammatory markers of women with severe obesity / Efeitos agudos de treinamento de força com diferentes intensidades sobre marcadores inflamatórios de mulheres com obesidade severa

ABSTRACT This study objective to compare the acute effects between one resistance training bout with high versus moderate intensities on inflammatory markers in women with severe obesity. Experimental crossover study, performed with adult women with severe obesity (BMI ≥ 40.0 kg/m²; age ≥ 18 years old). Each participant performed a high and moderate intensity resistance training (HIRT and MIRT, respectively) with an interval of 7 days between bouts. Four exercises were performed in the both protocols, with total training volume equalized. MIRT consisted of 3 sets of 8 repetitions each, with an intensity of 75% of 1RM, while HIRT consisted of 2 sets of 6 repetitions, followed by a 20-second rest, with a new performance of 2 to 3 repetitions, with one more rest of 20s and finishing with 2 to 3 more repetitions, at an intensity of 85% of 1RM. Blood samples were collected before, 15 minutes after and 24 hours after both training protocols. The inflammatory markers analyzed were IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ. Nine participants have completed the intervention (n=9; 35.2 ± 10.93 years old; BMI = 48.3 ± 5.06 kg/m²). The Mann-Whitney U test showed that there was no significant difference between the HIRT and MIRT in the concentration of markers. Friedman's test did not report significant differences between intragroup measures for the HIRT as well as MIRT. This research suggests that a single session of high or moderate intensity resistance training does not change the inflammatory status of women with severe obesity.

RESUMO Este estudo objetivou comparar os efeitos agudos entre uma sessão de treinamento de força de alta versus moderada intensidade sobre marcadores inflamatórios em mulheres com obesidade severa. Estudo experimental do tipo cross-over, realizado com mulheres adultas com obesidade severa (IMC ≥ 40,0 kg/m²; idade ≥ 18 anos). Cada participante realizou uma sessão de treinamento de força de alta e de moderada intensidade (HIRT e MIRT, respectivamente) com intervalo de 7 dias entre as sessões. Quatro exercícios foram realizados em ambos os protocolos, com volume total de treino equalizado. O MIRT consistiu em 3 séries de 8 repetições cada, com intensidade de 75% de 1RM, enquanto o HIRT consistiu em 2 séries de 6 repetições, seguidas de um descanso de 20 segundos, com nova execução de 2 a 3 repetições, com mais um descanso de 20s e finalização com mais 2 a 3 repetições, com intensidade de 85% de 1RM. Amostras de sangue foram coletadas antes, 15 minutos após e 24 horas após ambos os protocolos de treino. Os marcadores inflamatórios analisados foram IL-2, IL-4, IL-6, IL-10, TNF-α e IFN-γ. Nove participantes completaram a intervenção (n=9; 35,2 ± 10,93 anos; IMC = 48,3 ± 5,06 kg/m²). O teste U de Mann-Whitney mostrou que não houve diferença significativa entre HIRT e MIRT na concentração dos marcadores. O teste de Friedman não mostrou diferenças significativas entre as medidas intragrupo para HIRT e MIRT. Esta pesquisa sugere que uma única sessão de treinamento de força de alta ou moderada intensidade não altera o estado inflamatório de mulheres com obesidade severa.

The Effectiveness of Extra Virgin Olive Oil and the Traditional Brazilian Diet in Reducing the Inflammatory Profile of Individuals with Severe Obesity: A Randomized Clinical Trial.

We analyzed the effectiveness of two nutritional interventions alone and together, EVOO and the DieTBra, on the inflammatory profile of severely obese individuals. This study was an RCT with 149 individuals aged from 18 to 65 years, with a body mass index ≥ 35 kg/m2, randomized into three intervention groups: (1) 52 mL/day of EVOO (n = 50); (2) DieTBra (n = 49); and (3) DieTBra plus 52 mL/day of EVOO (DieTBra + EVOO, n = 50). The primary outcomes we measured were the-neutrophil-to-lymphocyte ratio (NLR) and the secondary outcomes we measured were the lymphocyte-to-monocyte ratio (LMR); leukocytes; and C reactive protein (CRP). After 12 weeks of intervention, DieTBra + EVOO significantly reduced the total leucocytes (p = 0.037) and LMR (p = 0.008). No statistically significant differences were found for the NLR in neither the intra-group and inter-group analyses, although a slight reduction was found in the DieTBra group (-0.22 ± 1.87). We observed reductions in the total leukocytes and LMR in the three groups, though without statistical difference between groups. In conclusion, nutritional intervention with DietBra + EVOO promotes a significant reduction in inflammatory biomarkers, namely leukocytes and LMR. CRP was reduced in EVOO and DieTBra groups and NLR reduced in the DieTBra group. This study was registered at ClinicalTrials.gov under NCT02463435.

Surgery for Obesity and Weight-Related Diseases Changes the Inflammatory Profile in Women with Severe Obesity: a Randomized Controlled Clinical Trial.

INTRODUCTION/PURPOSE: Obesity increases significantly every year worldwide. Since 1980, the prevalence of individuals with obesity has practically doubled. Obesity plays an important role in the pathophysiology of diseases that arise from a complex interaction of nutritional, genetic, and metabolic factors, characterizing a chronic inflammatory state. This study aimed to verify the systemic inflammatory response through the analysis of IGF-1, IL-23, and resistin levels and the lipid profile in severely obese women undergoing surgery for obesity and weight-related diseases. MATERIALS AND METHODS: This randomized controlled clinical trial includes female patients clinically diagnosed with severe obesity with an indication for bariatric surgery. RESULTS: In the initial evaluation, no significant difference was observed between the control (CG) and bariatric surgery (BSG) groups. The weight, BMI, systolic and diastolic blood pressures, total cholesterol, LDL, HDL, total non-HDL cholesterol, and glucose in BSG patients showed a significant change after surgery. Pre- and post-surgery levels of resistin, IGF-1, and IL-23 showed a significant difference in the BSG group, but only IL-23 was changed after 6 months in the CG. CONCLUSION: The results of this study confirmed that weight loss induced by surgery for obesity and weight-related diseases improved the lipid profile and reduced the chronic inflammatory status in women with severe obesity.

A Rare Potential Pathogenic Variant in the BDNF Gene is Found in a Brazilian Patient with Severe Childhood-Onset Obesity.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a pro-survival factor in the brain that also regulates energy balance. BDNF loss-of-function point mutations are responsible for haploinsufficiency, causing severe early-onset obesity. Up to date, only a few studies have sequenced this gene to search for rare mutations related to obesity. In this study, we aimed to investigate the prevalence of BDNF variants in a cohort of adults with severe obesity from Brazil. MATERIAL AND METHODS: This study comprised 201 adults with severe obesity (BMI ≥ 35.0 kg/m2) with onset during childhood- or adolescence/youth. As controls, 73 subjects with normal weight (18.5 ≤ BMI ≤ 24.9 kg/m2) were selected. The exclusion criteria were pregnancy, lactation, the use of medication to lose or gain weight, and the presence of symptoms suggestive of syndromic obesity (only for the case group). The coding region of the BDNF gene was screened by Sanger sequencing. Demographic, anthropometric, and blood pressure parameters were obtained from the participants as well as serum hormone and cytokines concentrations and biochemical values. RESULTS: As a result, three missense variants [p.(Thr2Ile), p.(Val66Met), and p.(Arg209Gln)] and four synonymous variants (p.Leu107=, p.Thr149=, p.Ala150=, and p.Ser213=) were identified. The p.(Arg209Gln) was predicted as pathogenic by all in silico algorithms used and was not observed in the control group. The individuals carrying the p.(Val66Met) mutated allele had higher waist circumference, HDL-cholesterol and MCP1 levels, and reduced risk of developing metabolic syndrome. CONCLUSION: We observed that the common BDNF p.(Val66Met) variant has influenced waist circumference, HDL-cholesterol, and MCP1 levels. This polymorphism has also a protective effect on metabolic syndrome susceptibility. Additionally, we described for the first time a rare potentially pathogenic BDNF variant in a Brazilian patient with severe obesity and childhood-onset.

Influence of Adherence to Social Distancing Due to the COVID-19 Pandemic on Physical Activity Level in Post-bariatric Patients.

We assessed physical activity using accelerometers and a questionnaire in 33 post-bariatric patients who reported to be adherent (n = 15) or not (n = 18) to social distancing due to the COVID-19 pandemic. Patients adherent to social distancing spent more time in sedentary behavior (1.1 h/day, 0.1, 2.2; p = 0.045) and less time in moderate-to-vigorous physical activity (- 12.2 min/day, - 23.8, - 0.6; p = 0.040) vs. non-adherent ones. Bland-Altman analysis comparing objective and subjective physical activity estimates showed a bias for time spent in sedentary behavior and moderate-to-vigorous activity of 2.8 h/day and 8.5 min/day. In conclusion, post-bariatric patients who were adherent to social distancing measures were more inactive and sedentary than non-adherent ones. Strategies to increase physical activity in post-bariatric patients exposed to social distancing are necessary during the COVID-19 pandemic.

Traditional Brazilian diet and extra virgin olive oil reduce symptoms of anxiety and depression in individuals with severe obesity: Randomized clinical trial.

RATIONAL & OBJECTIVE: Although the relationship between obesity, anxiety and depression is known, the clinical benefits of nutrition therapy in individuals with obesity have been scarcely studied. This study assessed the effectiveness of a traditional Brazilian diet (DieTBra) and extra virgin olive oil (EVOO) on the symptoms of anxiety and depression in severe obese participants. METHOD: This was a parallel randomized clinical trial in adults with severe obesity (Body Mass Index - BMI ≥ 35 kg/m2), DietBra Trial. Participants were randomized into three intervention groups in a ratio of 1: 1: 1 and followed up for 12 weeks. The three intervention groups were: 1) DieTBra, 2) 52 mL/day EVOO, and 3) DieTBra +52 mL/day EVOO. The symptoms of anxiety and depression were assessed by the Hospital Anxiety and Depression Scale. The outcome variables were: anxiety, depression and simultaneous anxiety and depression in the same individual. RESULTS: 149 severe obese individuals were randomized. The mean BMI was 46.3 ± 6.5 kg/m2 with a mean age of 38.9 ± 8.7 years. After randomization, individuals on medication for depression and anxiety were excluded, totaling 129 at baseline, with 44:43:42 per group. At the end of 12 weeks 113 individuals completed the study. There was a significant reduction of symptoms for the three groups: EVOO, DieTBra and DieTBra + EVOO, respectively: anxiety 38.23% (p = 0.019), 45.83% (p=<0.014), 33.33% (p < 0.013) depression 55.17% (p=<0.001), 50.00% (p=<0.007), 34.61% (p=<0.035), and anxiety/depression 57.69% (p=<0.001), 66.67% (p=<0.014), 27.78% (p=<0.013). CONCLUSIONS: Both DieTBra and olive oil interventions were effective in reducing symptoms of anxiety and depression in severe obese adults. These interventions can be integrated with clinical protocols for treatment of symptoms of anxiety and depression in severe obese individuals. TRIAL REGISTRATION: Clinicaltrials.gov NCT02463435.

Study of LEP, MRAP2 and POMC genes as potential causes of severe obesity in Brazilian patients.

PURPOSE: Monogenic forms of obesity are caused by single-gene variants which affect the energy homeostasis by increasing food intake and decreasing energy expenditure. Most of these variants result from disruption of the leptin-melanocortin signaling, which can cause severe early-onset obesity and hyperphagia. These mutation have been identified in genes encoding essential proteins to this pathway, including leptin (LEP), melanocortin 2 receptor accessory proteins 2 (MRAP2) and proopiomelanocortin (POMC). We aimed to investigate the prevalence of LEP, MRAP2 and POMC rare variants in severely obese adults, who developed obesity during childhood. To the best of our knowledge, this is the first study screening rare variants of these genes in patients from Brazil. METHODS: A total of 122 Brazilian severely obese patients (BMI ≥ 35 kg/m2) were screened for the coding regions of LEP, MRAP2 and POMC by Sanger sequencing. All patients are candidates to the bariatric surgery. Clinical characteristics were described in patients with novel and/or potentially pathogenic variants. RESULTS: Sixteen different variants were identified in these genes, of which two were novel. Among them, one previous variant with potentially deleterious effect in MRAP2 (p.Arg125Cys) was found. In addition, two heterozygous mutations in POMC (p.Phe87Leu and p.Arg90Leu) were predicted to impair protein function. We also observed a POMC homozygous 9 bp insertion (p.Gly99_Ala100insSerSerGly) in three patients. No pathogenic variant was observed in LEP. CONCLUSION: Our study described for the first time the prevalence of rare potentially pathogenic MRAP2 and POMC variants in a cohort of Brazilian severely obese adults. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity.

BACKGROUND: The melanocortinergic pathway orchestrates the energy homeostasis and impairments in this system often lead to an increase in body weight. Rare variants in the melanocortin 4 receptor (MC4R) gene resulting in partial or complete loss of function have been described with autosomal co-dominant inheritance. These mutations are the most common cause of non-syndromic monogenic obesity. In this context, this study aimed to sequence the MC4R gene in a Brazilian cohort of adults with severe obesity. METHODS: This study included 163 unrelated probands with Body Mass Index (BMI) ≥ 35 kg/m2, stratified into three groups, according to the period of obesity onset. From the total sample, 25 patients were enrolled in the childhood-onset group (0-11 years), 19 patients in the adolescence/youth-onset group (12-21 years), and 119 patients in the adult-onset group (>21 years). Blood pressure, anthropometric and biochemical characteristics were obtained, and the MC4R coding region of each subject's DNA was assessed using automated Sanger sequencing. RESULTS: Significant anthropometric differences between the groups were observed. Higher body weight and BMI medians were found in patients with childhood-onset or adolescence/youth-onset when compared to the adulthood-onset obesity group. A total of five mutations were identified, including four missense variants: p.Ser36Thr, p.Val103Ile, p.Ala175Thr, and p.Ile251Leu. Additionally, we observed one synonymous variant (p.Ile198=). The p.Ala175Thr variant was identified in a female case with severe obesity and adulthood-onset. This variant was previously described as a partial loss-of-function mutation, in which the minor allele poses dominant-negative effect, probably resulting in reduced cAMP activity. CONCLUSION: This study showed a prevalence of common and rare variants in a cohort of Brazilian adults with severe obesity and candidates to bariatric surgery. We have identified a rare potentially pathogenic MC4R variant in a Brazilian patient with severe and adulthood-onset obesity.