People With Obesity Research Articles

Improving obesity management: Insights from the ACTION Switzerland survey of people with obesity, physicians and dietitians.

ACTION Switzerland (NCT05232786) examined obesity-related perceptions, attitudes, behaviours and potential barriers to treatment among people with obesity (PwO) and healthcare professionals (HCPs). In March/April 2022, adult PwO (body mass index ≥30 kg/m2, per self-reported height/weight) and physicians/certified dietitians who manage PwO in Switzerland completed online surveys in a cross-sectional design. Overall, 1002 PwO, 125 physicians and 25 dietitians completed the survey. Most physicians (97%) and dietitians (100%), but only 57% of PwO, recognized obesity as a chronic disease. Only 42% of PwO considered themselves to have obesity/extreme obesity, while 61% who had discussed weight with an HCP reported receiving an obesity diagnosis. Many PwO (76%) believed weight loss was entirely their responsibility; physicians were less likely than dietitians to agree it was completely their patients' responsibility (28% vs. 68%). Physicians and dietitians report primarily initiating conversations about weight when patients have obesity-related comorbidities (85% and 64%); their top reasons for not discussing obesity were patients' perceived lack of motivation (76% and 60%) or interest (72% and 64%) in losing weight. In conclusion, some PwO are not aware that obesity is a chronic disease and incorrectly assume complete responsibility for weight loss. Improved communication between PwO and HCPs is required.

Anti-obesity treatment preferences of healthcare providers and people living with obesity: A survey-based study.

A cross-sectional, online survey was conducted in the United Kingdom, France, Germany, and the United States (14 November-22 December 2022) to investigate preferences for anti-obesity medication (AOM) among people with obesity (PwO) and healthcare providers (HCPs). Eligibility: Adult PwO who self-defined their body type as overweight/obese, were trying to lose weight and had BMI ≥30.0 or 27.0-29.9 kg/m2 with ≥1 obesity-related complication; HCPs had to see ≥30 PwO in a typical month and be a decision-maker regarding their weight loss. The survey included 2500 PwO and 500 HCPs. Exercise (96%) and diet (90%) were the most common weight management methods; AOM use was low (8%). Key barriers to use of prescribed AOMs among PwO were not wanting to take AOM (34%), side effects concerns (33%), and not trusting AOM (26%). Most HCPs (79%) had prescribed/recommended AOMs. Efficacy was the most common reason for preferring one of the shown product profiles among PwO (60%) and HCPs (86%); improving cardiovascular risk was also important to 95% of HCPs when deciding which AOM to prescribe. AOM preference is largely driven by efficacy. Increasing knowledge could help to address barriers to AOM use and improve outcomes for PwO.

Sex differences in perceived discrimination among patients with obesity.

The negative impacts of perceived discrimination on health have been documented, but how perceptions of discrimination vary by sex among people with obesity (PWO) is not well understood. This study assessed sex differences in perceived discrimination among PWO. This cross-sectional study analysed self-reported data from racially/ethnically diverse PWO attending an academic obesity program. The primary outcome was perceived discrimination, assessed by the Major Experiences of Discrimination (MED) and Everyday Discrimination Scale (EDS). Sex differences were evaluated by univariate and multivariable regression analysis adjusted for key descriptive variables. The final analytical sample included 60 PWO (62% female, 61% non-Hispanic white (NHW), 12% Hispanic, 39% non-Hispanic black (NHB), mean age 53 years, mean BMI 34 kg/m2). Women experienced everyday discrimination 59% less than men but this was not significant (OR 0.41; 95% CI 0.08-2.16; p = .29). Participant highest BMI was correlated with acute discrimination (total MED score) (r = 0.39; p = .0024) and chronic discrimination (total EDS score) (r = 0.28; p = .03). Most participants reported more chronic discrimination compared to acute discrimination (85% vs. 48%). Mean MED (β -0.18; 95% CI -0.93 to +0.56; p = .62) and EDS scores (β -0.25; 95% CI -3.37 to +2.87; p = .87) were not significantly different between women and men. Perceived discrimination was common and experienced equally between men and women with obesity. Incorporating discrimination experiences into obesity care models may be an important step to improving quality of care and outcomes.

Early versus late-onset of weight struggles among patients with obesity: Data from the ACTION-IO study

ABSTRACT Background and Aim: The prevalence of obesity is increasing and people with obesity (PwO) continue to struggle with their weight. We aimed to describe the experiences of people who struggled with their weight at an early age (EAO) or at a later age (LAO), their discussions with their healthcare practitioners (HCPs) and episodes of depression and anxiety. Methods: We gathered information from 1,000 adults PwO, categorized them into EAO and LAO and analyzed their responses regarding weight loss attempts, discussions with their HCP, perceptions about obesity and episodes of depression/anxiety. Results: Mean age was 36.6 years old, and 73.0% were AAO. EAO had significantly fewer weight loss attempts and had fewer interactions with their HCP. EAO reported less HCP support for weight management, were less motivated to lose weight, and experienced more episodes of anxiety/depression. Significant association between greater obesity class with longer duration of weight problems, and depression and anxiety. EAO PwOs were less likely to discuss weight problems with their HCP. Conclusion: It is fundamental that HCPs recognize and address weight issues in PwO who are at risk of obesity in adulthood as early as adolescence. They should also take the lead in addressing these psychophysiological concerns by involving the parents in the decision-making process and facilitating shared planning. These may enhance their motivation to lose weight, boost self-confidence, and reduce the complications of obesity.

Erythrocyte Oxidative Status in People with Obesity: Relation to Tissue Losses, Glucose Levels, and Weight Reduction.

This study aimed to investigate the impact of reductions in various body mass components on the erythrocyte oxidative status and glycemic state of people with obesity (PWO). A total of 53 PWO followed a six-month individualized low-calorie diet with exercise, during which anthropometric, biochemical, and oxidative parameters were measured. The participants were divided into groups based on weight (W), visceral fat area (VFA), total body water (TBW), and skeletal muscle mass (SMM) losses, as well as normoglycemia (NG) and hyperglycemia (HG). Weight reduction normalized glycemia and influenced erythrocyte enzyme activity. Regardless of the tissue type lost (VFA, TBW, or SMM), glutathione peroxidase activity decreased in all groups, accompanied by an increase in glutathione reductase activity. Lipofuscin (LPS) and malondialdehyde (MDA) concentrations decreased regardless of the type of tissue lost. The α-/γ-tocopherol ratio increased in those losing >10% body weight, >15% VFA, and >5% TBW. In the NG group, compared to the HG group, there was a decrease in glutathione peroxidase and an increase in glutathione reductase, with these changes being stronger in the HG group. The LPS and MDA concentrations decreased in both groups. Significant correlations were observed between glucose reduction and changes in catalase, retinol, and α-tocopherol, as well as between VFA reduction and changes in vitamin E, L-LPS, and the activities of L-GR and L-GST. This analysis highlights the complex interactions between glucose metabolism, oxidative state, and erythrocyte membrane integrity, crucial for understanding diabetes and its management. This study shows the significant metabolic adaptability of erythrocytes in response to systemic changes induced by obesity and hyperglycemia, suggesting potential therapeutic targets to improve metabolic health in obese individuals.

Impact of Sleeve Gastrectomy on Brain Structural Integrity.

Potential brain structural differences in people with obesity (PwO) who achieve over or less than 50% excess weight loss (EWL) after sleeve gastrectomy (SG) are currently unknown. We compared measures of gray matter volume (GMV) and white matter (WM) microstructural integrity of PwO who achieved over or less than 50% EWL after SG with a group of controls with obesity (CwO) without a past history of metabolic bariatric surgery. Sixty-two PwO underwent 1.5T MRI scanning: 24 who achieved more than 50% of EWL after SG ("group a"), 18 who achieved less than 50% EWL after SG ("group b"), and 20 CwO ("group c"). Voxel-based morphometry and tract-based spatial Statistics analyses were performed to investigate GMV and WM differences among groups. Multiple regression analyses were performed to investigate relationships between structural and psychological measures. Group a demonstrated significantly lower GMV loss and higher WM microstructural integrity with respect to group b and c in some cortical regions and several WM tracts. Positive correlations were observed in group a between WM integrity and several psychological measures; the lower the WM integrity, the higher the mental distress, emotional dysregulation, and binge eating behavior. The present results gain a new understanding of the neural mechanisms of outcome in patients who undergo SG. We found limited GMV changes and extensive WM microstructural differences between PwO who achieved over or less than 50% EWL after SG, which may be due to higher vulnerability of WM to the metabolic dysfunction present in PwO.

ACTION-FRANCE: Insights into Perceptions, Attitudes, and Barriers to Obesity Management in France

Background/Objectives: ACTION-FRANCE (Awareness, Care, and Treatment In Obesity maNagement in France) aims to identify the perceptions, attitudes, behaviors, and potential barriers to effective obesity management in France and guide collaborative actions. Methods: ACTION-FRANCE is a cross-sectional survey of people with obesity (PwO) and healthcare professionals (HCPs) in France. The PwO and HCP survey questionnaire periods ran from 27 September 2022 to 1 February 2023 and from 19 December 2022 to 31 March 2023, respectively. Results: The study, encompassing 1226 PwO and 166 HCPs, reveals a shared recognition of obesity as a chronic condition. However, despite being requested by most PwO, weight-related discussions are surprisingly infrequent, leading to delayed diagnosis and care. PwO and HCPs held different views as to why: HCPs often attributed it to PwO’s lack of motivation or disinterest, whereas PwO avoided them because they felt weight management was their own responsibility and were uncomfortable discussing it. When weight was discussed, primarily with general practitioners (GPs), discussions mostly focused on physical activity and diet. However, results identified the strong psychosocial impact of obesity: 42% of respondents reported anxiety/depressive symptoms, and many more hesitated to engage in certain social activities because of their weight. Psychotherapy was only discussed by 55% of HCPs. Pharmaceutical options were also rarely discussed (19.5% of HCPs), though 56.1% of PwO reported they would want to. Conclusions: HCPs’ and PwO’s perceptions differed significantly and need to converge through enhanced communication. A holistic approach, integrating comprehensive training for GPs and recognizing psychological comorbidities, would help to bridge perceptual gaps effectively and foster more empathetic and effective patient care.

609-P: Effects of Oligomalt (OM), a New Slowly Digestible Carbohydrate (SDC), on Postprandial (PP) Glucose, Insulin, and GLP-1 Trajectories Compared with Maltodextrin (MD) in People with Obesity (PwO) or Type 2 Diabetes (T2D)—A Double-Blind RCT

609-P: Effects of Oligomalt (OM), a New Slowly Digestible Carbohydrate (SDC), on Postprandial (PP) Glucose, Insulin, and GLP-1 Trajectories Compared with Maltodextrin (MD) in People with Obesity (PwO) or Type 2 Diabetes (T2D)—A Double-Blind RCT

Features and behaviours for weight loss in the Chilean cohort with obesity from the ACTION study.

In Latin America, obesity rates are among the highest in the world. Currently, people with obesity (PWO) receive suboptimal care due to several challenges and barriers. The international ACTION-IO study aimed to identify perceptions, attitudes and behaviours of PWO and healthcare providers (HCP), and to assess potential barriers to effective obesity care. The aim of this subanalysis of the Chilean cohort was to compare their characteristics, perceptions, attitudes and behaviours according to the percentage of weight loss (lower weight loss [LWL; ≤10%] or higher weight loss [HWL; >10%] of basal weight). The ACTION-IO survey was completed by 1000 Chilean PWO and 200 HCPs. Mean age of PWO was 38 years (range 18-75); 62% were female. The majority had class I obesity. HWL subgroup represented 17.2% of all Chilean subset. Specific characteristics of patients with HWL were identified (higher educational level, lower proportion of class III obesity, preference for consulting obesity specialists, considering conversations with HCP as very helpful). HWL patients reported higher rates of favourable outcomes following HCP advice and a higher probability of attending scheduled follow-up visits. Certain demographic and behavioural variables (educational level, consultation to obesity specialists, adherence to HCP advice, follow-up scheduled visits and becoming aware of the obesity state) may identify PWO with a higher probability of a greater weight loss.

ACTION APAC: Understanding perceptions, attitudes and behaviours in obesity and its management across south and Southeast Asia.

To identify perceptions and attitudes among people with obesity (PwO) and healthcare professionals (HCPs) toward obesity and its management in nine Asia-Pacific (APAC) countries, a cross-sectional online survey was conducted among adult PwO with self-reported body mass index of ≥25 kg/m2 (≥27 kg/m2, Singapore), and HCPs involved in direct patient care. In total, 10 429 PwO and 1901 HCPs completed the survey. Most PwO (68%) and HCPs (84%) agreed that obesity is a disease; however, a significant proportion of PwO (63%) and HCPs (41%) believed weight loss was the complete responsibility of PwO and only 43% of PwO discussed weight with an HCP in the prior 5 years. Most respondents acknowledged that weight loss would be extremely beneficial to PwO's overall health (PwO 76%, HCPs 85%), although nearly half (45%) of PwO misperceived themselves as overweight or of normal weight. Obesity was perceived by PwO (58%) and HCPs (53%) to negatively impact PwO forming romantic relationships. HCPs cited PwOs' lack of interest (41%) and poor motivation (37%) to lose weight as top reasons for not discussing weight. Most PwO (65%) preferred lifestyle changes over medications to lose weight. PwO and HCPs agreed that lack of exercise and unhealthy eating habits were the major barriers to weight loss. Our data highlights a discordance between the understanding of obesity as a disease and the actual behaviour and preferred approaches to manage it among PwO and HCPs. The study addresses a need to align these gaps to deliver optimal care for PwO.

Short-term effects of semaglutide among patients with obesity with and without food addiction: an observational study

Introduction Food addiction (FA) is highly prevalent among people with obesity (PwO) and may constitute a key factor in weight loss failure or weight regain. GLP-1 analogues have been shown to act on the mesolimbic system, which is related to hedonic overeating and substance abuse. We aimed to study the effects of low doses of semaglutide on FA symptomatology and to evaluate whether the presence of FA have a negative impact on weight loss despite treatment with semaglutide. Methods One hundred and thirteen PwO (45.5 ± 10.2 years) were evaluated anthropometrically baseline and after four months of treatment with semaglutide. PwO were evaluated for the presence of FA by completing The Spanish version of the Yale Food Addiction Scale 2.0 questionnaire (YFAS 2.0). Results Baseline BMI and fat mass (%) were greater among PwO with FA (35.8 ± 4.5 vs 33 ± 3.9 kg/m2and 44.2 ± 6.5 vs 40.1 ± 7.9%; p = .01). After four months of treatment with semaglutide, the prevalence of FA diminished from 57.5% to 4.2% (p < .001). The percentage of weight loss (6.9 ± 12.7 vs 5.3 ± 4.6%; p = .4) and the proportion of fat mass loss (2 ± 9 vs 1.6 ± 3.1%; p = .7) were comparable between PwO with and without FA. No differences regarding side effects and treatment discontinuations were seen between the two groups Conclusion Semaglutide is an effective tool for the amelioration of FA symptomatology among PwO. Despite PwO with FA had greater basal BMI and fat mass, semaglutide showed similar results compared to PwO without FA in terms of weight and fat mass loss at short term.

Does the Prevalence of Obesity in the Different Regions of Spain Influence the Attitudes, Perception, and Barriers to Its Treatment?

Introduction: The differences in the prevalence of obesity between the various regions of Spain, partly attributed to socioeconomic differences, may influence the approach to this disease. The aim of this study was to compare differences in attitudes, perception, and barriers to the treatment of obesity between people with obesity (PwO) and health care professionals (HCPs), between the different regions of Spain. Methods: Sub-analysis of the ACTION-IO Spain study, which included 1,500 PwO and 306 HCP, was performed to identify differences in PwQ and HCPs belonging to regions with high prevalence of obesity (>16%, n = 9 regions, high prevalence of obesity [HPO] group) and low prevalence of obesity (<16%, n = 8 regions, low prevalence of obesity [LPO] group) (self-reported data), according to the 2017 National Health Survey of Spain. Statistics: comparison of proportions (χ2). Results: A total of 746 PwO belonged to HPO and 754 to LPO group. The PwO in HPO group were younger, had lower income, a lower level of higher education, higher unemployment rate, and fewer comorbidities. Obesity was considered a chronic disease to a higher extent in HPO compared to LPO group (62 vs. 56%), but this difference was not statistically significant. The PwO in HPO group discussed less with the HCPs about their excess weight (57 vs. 70%), did not feel motivated to lose weight in a higher percentage (26 vs. 18%), and felt less emotionally supported (16 vs. 24%). In HPO group, the preference for unhealthy food (51 vs. 36%), and the costs of healthy eating, anti-obesity drugs and bariatric surgery were perceived barriers to losing weight. A higher proportion of PwO in HPO group considered that exercise (58 vs. 40%) was more effective for achieving weight loss. In contrast, LPO group considered diet more effective (48 vs. 32%). HCPs in HPO group felt more motivated to treat obesity (83 vs. 68%) and a higher proportion (14 vs. 5%) identified the economic burden as one of the main reasons why PwO do not start conversations to lose weight. Conclusions: There is less concern and conversation about excess weight in PwO in regions with a higher prevalence of obesity, with socioeconomic limitations being one of the main perceived barriers to treatment.

The GLP-1 analogue battle: effects of semaglutide 0,5 mg/weekly versus liraglutide 3 mg/daily on anthropometric parameters after 3 months in a real world-scenario

the prevalence of obesity is reaching a pandemic status. The SCALE trials showed that liraglutide 3 mg among people with obesity (PwO) was effective to reduce bodyweight and related complications. The fact that almost two-thirds of patients did not achieve the desired weight loss with the maximum dose of liraglutide made almost mandatory the development of other pharmacological options. The STEP 1-5 trials showed the effectiveness of semaglutide in reducing bodyweight in a dose-dependent manner. Moreover, the STEP 8 trial proved the superiority of semaglutide 2,4 mg/week versus liraglutide 3 mg/daily. We aimed to assess the effects of subcutaneous (s.c.) semaglutide 0.5 mg/weekly compared with s.c. liraglutide 3 mg/daily in PwO on anthropometric parameters in a real world-scenario for 3 months. we retrospectively evaluated 179 PwO (91.9 % ♀, 45.7 ± 10 years, and 33.3 ± 7 kg/m2) who received treatment with aGLP-1 as add-on therapy to lifestyle interventions. Patients were evaluated at baseline and after 3 months. Ninety-nine patients were prescribed s.c. semaglutide 0.5 mg/weekly with an off-label indication for weight reduction. These patients were compared with 80 patients treated with s.c. liraglutide 3 mg/daily. The main reason for prescribing of s.c. semaglutide was economic. Body composition was evaluated using a bioimpedance device (Tanita MC 580M®). baseline weight was significantly greater with semaglutide compared to liraglutide (97.19 ± 21.09 vs. 90.73 ± 21.88 kg; p < 0.01) as was fat mass (42.43 ± 15.04 vs. 34.84 ± 16.07 kg; p < 0.01), whereas baseline lean mass was lesser among subjects treated with semaglutide (31.62 ± 7.56 vs 45.69 ± 15.51 kg; p < 0.01). PwO experienced a significant reduction in weight using s.c. semaglutide 0.5 mg/weekly (96.67 ± 20.83 vs. 91.44 ± 19.6 kg; p < 0.01) or s.c. liraglutide 3 mg/daily (90.73 ± 21.88 vs. 80.13 ± 18.38 kg; p < 0.01) No significant differences were seen between the amount of weight lost (5.28 ± 4.22 vs 5.72 ± 1.62 kg; p = 0.5) in the two groups. Furthermore, both groups were comparable in fat mass (2.69 ± 5.34 vs 0.96 ± 4.22 kg; p = 0.3) and fat-free mass (0.86 ± 1.63 vs 1.03 ± 0.94 kg; p = 0.07) after 3 months of treatment with both aGLP1. Side effects were gastrointestinal and transient/comparable between groups Conclusions: subcutaneous semaglutide 0.5 mg and subcutaneous liraglutide 3 mg are effective treatments for reducing weight safely among PwO in a real-world scenario at short term and without a negative impact on fat-free mass. Moreover, low doses of semaglutide were similar to liraglutide 3 mg in reducing bodyweight at short term.

A multifaceted training tool to reduce weight bias among healthcare students: A randomized controlled trial

BackgroundWeight bias toward people with obesity (PwO) is common in healthcare settings. Efforts to address weight bias in healthcare settings should begin during university studies. This study aimed to explore the effect of a multifaceted intervention on weight bias among undergraduate healthcare students. MethodsAn open label randomized controlled trial. The intervention tool consisted of short video lectures on obesity, vignettes simulating interactions between health professionals and PwO, and open discourse with a PwO. The control group received a short-written document on obesity. Online questionnaires on Anti-Fat Attitudes ('AFA'), short form of the Fat-Phobia Scale ('FPS'), Weight Implicit Association Test ('Weight-IAT'), and knowledge about obesity were administered at baseline, 1-week, and 6-week post-intervention. ResultsA total of 162, 152, and 146 students participated in the study at baseline, 1-week, and 6-week post-intervention, respectively. Their mean age was 25.8 ± 6.7 years and 88.3% were women. Means of AFA total scores and FPS scores decreased significantly over time only within the intervention group (P Time*Group = 0.002 and 0.014). Both groups showed a similar trend over time in mean scores of Weight-IAT (P Time*Group = 0.868) and knowledge about obesity (P Time*Group = 0.115). ConclusionsA multifaceted intervention resulted in a significant reduction in explicit weight bias but did not yield any additional advantages over the control group in implicit weight bias and knowledge about obesity. ClinicalTrials.gov numberNCT05482802.

Differences in the cluster of depressive symptomatology among bariatric surgery candidates, long-term bariatric surgery patients, and subjects with a major depressive disorder without obesity.

depression is more frequent among people with obesity (PwO) compared to the general population. Depression seems to improve after bariatric surgery (BS) at short term, but data are inconclusive at long term. Besides, it is not known whether depressive symptoms among PwO are similar to those people with a major depression without obesity. we aimed to study whether there are differences regarding depressive symptomatology among subjects seeking BS or patients after BS in the long-term compared with subjects with MDD. the Beck Depression Inventory (BDI) was administered to three groups: 52 patients seeking BS (OB), 135 patients with a BS with a minimum follow-up of 18 months (BS) and 45 subjects with a MDD (MDD). the MDD obtained the higher score with the BDI whether compared to the OB (18.9 ± 12.7 vs 14.2 ± 6.9; p = 0.01) or the BS (18.9 ± 12.7 vs 8.1 ± 8; p < 0.0001). Also, BS presented a lower BDI than the OB (8.1 ± 8 vs 14.2 ± 6.9; p < 0.0001). The MDD scored higher in the psychological domain than patients in the OB (9.9 ± 7.5 vs 5.7 ± 5.1; p < 0.0001) as well as in the BS (9.9 ± 7.5 vs 3.1 ± 3; p < 0.0001). There was a negative correlation between a greater score in the somatic domain and %EPP (p = 0.04). at long term, depressive symptomatology among subjects with a BS remained lower compared to PwO seeking BS.PwO presented a different cluster of depression compared to individuals with a MDD. BS reduces the somatic depressive cluster at long term, although its presence is associated to a lesser weight loss.

Serum Oxidative Status in People with Obesity: Relation to Tissue Losses, Glucose Levels, and Weight Reduction.

This work aims to study the effect of reductions in various body mass components on the oxidative, glycemic, and lipid parameters of people with obesity (PWO). A total of 53 PWO underwent a six-month individualized low-calorie diet combined with moderate exercise, during which anthropometric, biochemical, and oxidative parameters were measured. Probands were divided into groups based on weight, visceral fat area (VFA), total body water (TBW), and skeletal muscle mass (SMM) losses. Weight reduction normalizes glycemia, but VFA reduction is less pronounced, while SMM and TBW reductions are more pronounced in patients with higher initial concentrations of glucose and fructosamine. Moreover, changes in oxidative parameters correlate with changes in glucose. Weight loss, regardless of the reduced tissue, decreases cardiovascular risk. We observed a significant change in almost all parameters related to the redox state. In general, parameters responsible for antioxidant action improved, and markers of oxidative damage decreased. Malondialdehyde, lipid peroxides, and total oxidative status levels can be considered biomarkers reflecting only the current severity of reactive oxygen species genesis processes. When considering the glycemic state, the results are not as clear due to the substantial differences between normoglycemic and hyperglycemic patients. Glycemic status is a factor playing a crucial role in weight reduction.

127-OR: The Effect of Tirzepatide during Weight Loss on Metabolic Adaption, Fat Oxidation, and Food Intake in People with Obesity

We hypothesized that tirzepatide (TZP) causes body weight loss by reducing food intake and, according to pre-clinical studies, decreasing metabolic adaptation during weight loss. In a randomized blinded clinical trial in people with obesity (PWO) undergoing caloric restriction, we investigated the effect of TZP vs Placebo (PBO) on energy metabolism after targeting a 10% (±2%) weight loss. In this 18wk phase 1 study, 55 PWO, were randomized (1:1) to TZP 15 mg or PBO (mean baseline body weight 102.5 vs 103.1 kg, respectively). The primary objective was to investigate the change from baseline in sleeping metabolic rate (SMR) measured by whole-room indirect calorimetry. Secondary measures were changes in 24-hr sedentary energy expenditure, 24-hr respiratory quotient (RQ), sleeping RQ, substrate utilization, body composition (BC) and food intake. TZP caused greater weight loss than PBO (-16.7 kg vs -8.3 kg; p&amp;lt;0.001). The decreases in SMR and 24-hr energy expenditure were not different between groups after adjusting for changes in body weight and BC. However, TZP significantly reduced 24-hr RQ and sleeping RQ compared to PBO; thus, significantly increasing fat oxidation while decreasing carbohydrate and protein oxidation rates. TZP also significantly reduced food intake. Overall, TZP did not affect metabolic adaptation but significantly increased fat oxidation. Disclosure E.Ravussin: Advisory Panel; Novartis, Research Support; Eli Lilly and Company, Novartis AG. A.Haupt: Employee; Lilly, Stock/Shareholder; Lilly. G.Sanchez-delgado: Research Support; Eli Lilly and Company, Novo Nordisk, Abbott, Maastricht instruments, Vyaire Medical, ParvoMedics, Cosmed, Speaker's Bureau; Eli Lilly and Company. C.K.Martin: Board Member; EHE Health, Wondr Health, Other Relationship; ABGIL, Research Support; Pack Health, Evidation Health, Lilly, WW International, Inc. H.Nishiyama: None. J.Li: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. S.Urva: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. E.J.Pratt: Employee; Eli Lilly and Company. T.Coskun: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Z.Milicevic: Employee; Eli Lilly and Company. Funding Eli Lilly and Company

Glucagon-like peptide-1 therapy in people with obesity restores natural killer cell metabolism and effector function.

People with obesity (PWO) have functionally defective natural killer (NK) cells, with a decreased capacity to produce cytokines and kill target cells, underpinned by defective cellular metabolism. It is plausible that the changes in peripheral NK cell activity are contributing to the multimorbidity in PWO, which includes an increased risk of cancer. This study investigated whether therapy with long-acting glucagon-like peptide-1 (GLP-1) analogues, which are an effective treatment for obesity, could restore NK cell functionality in PWO. In a cohort of 20 PWO, this study investigated whether 6 months of once weekly GLP-1 therapy (semaglutide) could restore human NK cell function and metabolism using multicolor flow cytometry, enzyme-linked immunosorbent assays, and cytotoxicity assays. These data demonstrate that PWO who received GLP-1 therapy have improved NK cell function, as measured by cytotoxicity and interferon-γ/granzyme B production. In addition, the study demonstrates increases in a CD98-mTOR-glycolysis metabolic axis, which is critical for NK cell cytokine production. Finally, it shows that the reported improvements in NK cell function appear to be independent of weight loss. The restoration, by GLP-1 therapy, of NK cell functionality in PWO may be contributing to the overall benefits being seen with this class of medication.

Oxidative Damage by 3-nitrotyrosine in Young Adults with Obesity: Its Implication in Chronic and Contagious Diseases.

Cellular damage by oxidation occurs in numerous chronic diseases, such as obesity, type II diabetes, cardiovascular disease, nonalcoholic fatty liver, etc. The oxidized compound 3-nitrotyrosine is a marker of oxidative stress and protein oxidation damage. The article aims to assess whether 3-nitrotyrosine levels are higher in young people with obesity than in the same population without obesity. Anthropometry and blood chemistry analyses were performed on 24 young Mexican participants (18-30 years old), categorized into two groups based on their waist circumference: Withobesity (≥ 80 cm women; ≥ 90 cm men) and without-obesity (<80 cm women; <90 cm men). Additionally, 3-nitrotyrosine blood values were quantified by ELISA. Except for HDL-cholesterol, the mean values of lipids increased in women and men with obesity (p<0.05), and 3-nitrotyrosine concentration (nM/μg total protein) was higher by 60% in the group with-obesity compared to the group without-obesity, both for women (66.21 ± 23.85 vs. 40.69 ± 16.25, p<0.05) and men (51.72 ± 20.56 vs. 30.52 ± 5.21, p<0.05). Oxidative damage measured by compound 3-nitrotyrosine was higher in the group with obesity than in the group without obesity, which, if not controlled, could lead to a chronic oxidative condition and thereby to a degree of cellular aging with adverse health effects.

Antigen specific T cells in people with obesity at five months following ChAdOx1 COVID-19 vaccination.

People with obesity (PWO) face an increased risk of severe outcomes from COVID-19, including hospitalisation, ICU admission and death. Obesity has been seen to impair immune memory following vaccination against influenza, hepatitis B, tetanus, and rabies. Little is known regarding immune memory in PWO following COVID-19 adenovirus vector vaccination. We investigated SARS-CoV-2 specific T cell responses in 50 subjects, five months following a two-dose primary course of ChAdOx1 nCoV-19 (AZD1222) vaccination. We further divided our cohort into PWO (n = 30) and matched controls (n = 20). T cell (CD4+, CD8+) cytokine responses (IFNγ, TNFα) to SARS-CoV-2 spike peptide pools were determined using multicolour flow cytometry. Circulating T cells specific for SARS-CoV-2 were readily detected across our cohort, with robust responses to spike peptide stimulation across both T cell lines. PWO and controls had comparable levels of both CD4+ and CD8+ SARS-CoV-2 spike specific T cells. Polyfunctional T cells - associated with enhanced protection against viral infection - were detected at similar frequencies in both PWO and controls. These data indicate that PWO who have completed a primary course of ChAdOx1 COVID-19 vaccination have robust, durable, and functional antigen specific T cell immunity that is comparable to that seen in people without obesity.