A human omentum-specific mesothelial-like stromal population inhibits adipogenesis through IGFBP2 secretion.

Adipose tissue plasticity is orchestrated by molecularly and functionally diverse cells within the stromal vascular fraction (SVF). Although several mouse and human adipose SVF cellular subpopulations have by now been identified, we still lack an understanding of the cellular and functional variability of adipose stem and progenitor cell (ASPC) populations across human fat depots. To address this, we performed single-cell and bulk RNA sequencing (RNA-seq) analyses of >30 SVF/Lin- samples across four human adipose depots, revealing two ubiquitous human ASPC (hASPC) subpopulations with distinct proliferative and adipogenic properties but also depot- and BMI-dependent proportions. Furthermore, we identified an omental-specific, high IGFBP2-expressing stromal population that transitions between mesothelial and mesenchymal cell states and inhibits hASPC adipogenesis through IGFBP2 secretion. Our analyses highlight the molecular and cellular uniqueness of different adipose niches, while our discovery of an anti-adipogenic IGFBP2+ omental-specific population provides a new rationale for the biomedically relevant, limited adipogenic capacity of omental hASPCs.

[Focus on obesity drug treatments]. / Focus sur les traitements médicamenteux de l'obésité.

The management of obesity is changing dramatically with the emergence of new drug treatments. Glucagon-like peptide-1 (GLP-1) receptor agonists are approved for this indication in Switzerland, and approval is currently being sought for a GLP-1 and glucose-dependent insulinotropic polypetide (GIP) co-agonist. Reimbursement conditions are restrictive, and patients are given only one opportunity to achieve the weight loss required for continued reimbursement. The popularity of these treatments has led to worldwide stock-outs for several months now, and it is essential that prescribers respect the indications so as not to prejudice obese patients. This article provides a review of the treatments available and the conditions under which they are reimbursed, as well as those that should be reimbursed soon.

La prise en charge de l'obésité est profondément modifiée par l'essor de nouveaux traitements médicamenteux. Les agonistes du récepteur du glucagon-like peptide-1 (GLP-1) sont approuvés dans cette indication en Suisse et une approbation est en cours d'analyse pour un coagoniste du GLP-1 et du glucose-dependent insulinotropic polypetide (GIP). Les conditions de remboursement sont cependant strictes et les patients ne bénéficient que d'une seule opportunité pour obtenir les pertes pondérales qui autorisent la poursuite du remboursement. La popularité de ces traitements occasionne des ruptures de stocks depuis plusieurs mois au niveau mondial et il est essentiel que les prescripteurs respectent les indications afin de ne pas prétériter les patients en situation d'obésité. Cet article propose un rappel des traitements disponibles et les conditions encadrant leur remboursement, ainsi que ceux qui le seront prochainement.

[Pregnancy and bariatric surgery : from pre-conception to postpartum]. / Grossesse et chirurgie bariatrique : du préconceptionnel au postpartum.

Bariatric surgery is regularly offered to women of childbearing age. Pregnancy after such surgery should be planned and requires special attention. Some complications associated with obesity during pregnancy are reduced after bariatric surgery, but reduced dietary intake and malabsorption can cause nutritional deficiencies, that need to be carefully screened for and supplemented. Dietary management is recommended, and any unusual abdominal pain should be referred to a bariatric surgeon. We offer a summary of recommendations for appropriate follow-up of these pregnancies.

La chirurgie bariatrique est régulièrement proposée à des femmes en âge de procréer. Une grossesse après une telle chirurgie devrait être planifiée et demande une attention particulière. Certaines complications liées à l'obésité durant la grossesse sont réduites après une chirurgie bariatrique mais une diminution des apports alimentaires et la malabsorption peuvent engendrer des carences nutritionnelles qui doivent être attentivement dépistées et supplémentées. Une prise en charge diététique est recommandée et toute douleur abdominale inhabituelle doit faire demander l'avis d'un chirurgien bariatrique. Nous proposons une synthèse des recommandations pour un suivi adéquat de ces grossesses.

cGAS-STING drives ageing-related inflammation and neurodegeneration.

Low-grade inflammation is a hallmark of old age and a central driver of ageing-associated impairment and disease1. Multiple factors can contribute to ageing-associated inflammation2; however, the molecular pathways that transduce aberrant inflammatory signalling and their impact in natural ageing remain unclear. Here we show that the cGAS-STING signalling pathway, which mediates immune sensing of DNA3, is a critical driver of chronic inflammation and functional decline during ageing. Blockade of STING suppresses the inflammatory phenotypes of senescent human cells and tissues, attenuates ageing-related inflammation in multiple peripheral organs and the brain in mice, and leads to an improvement in tissue function. Focusing on the ageing brain, we reveal that activation of STING triggers reactive microglial transcriptional states, neurodegeneration and cognitive decline. Cytosolic DNA released from perturbed mitochondria elicits cGAS activity in old microglia, defining a mechanism by which cGAS-STING signalling is engaged in the ageing brain. Single-nucleus RNA-sequencing analysis of microglia and hippocampi of a cGAS gain-of-function mouse model demonstrates that engagement of cGAS in microglia is sufficient to direct ageing-associated transcriptional microglial states leading to bystander cell inflammation, neurotoxicity and impaired memory capacity. Our findings establish the cGAS-STING pathway as a driver of ageing-related inflammation in peripheral organs and the brain, and reveal blockade of cGAS-STING signalling as a potential strategy to halt neurodegenerative processes during old age.

Impact of Preoperative Psychiatric Profile in Bariatric Surgery on Long-term Weight Outcome.

BACKGROUND: Conflicting results have been reported regarding the predictive value of preoperative psychological assessment and weight outcome after bariatric surgery. This might be attributed to different factors affecting early weight loss and long-term weight loss. Herein, we investigated whether preoperative psychiatric profile was associated with preoperative BMI and with both early (1 year) and long-term (5 years) weight loss after Roux-en-Y gastric bypass (RYGB). METHODS: Prospective observational cohort study of patients undergoing RYGB between 2013 and 2019. Symptoms related to anxiety, depression, eating disorder, and alcohol use disorders were assessed by employing validated, specific psychometric tests (STAI-S/T, BDI-II, BITE, AUDIT-C) prior to surgery. Pre-operative BMI, early weight loss (1 year), and long-term weight evolution (up to 5 years) were registered. RESULTS: Two hundred thirty six patients (81% women) were included in the present study. Linear longitudinal mixed model showed a significant effect of preoperative high anxiety (STAI-S) on long-term weight outcome, after controlling for gender, age and type 2 diabetes. Patient with high preoperative anxiety score regained weight faster than those experiencing low anxiety (each year percent excess BMI loss (%EBMIL) - 4.02%, ± 1.72, p = 0.021). No other pre-operative psychiatric symptoms have been shown to have an impact on long-term weight loss. In addition, no significant association was found between any of the pre-operative psychiatric variables and pre-operative BMI, or early weight loss (%EBMIL) at 1-year post-RYGB. CONCLUSION: Herein we identified high anxiety score (STAI-S) as a predictor for long-term weight regain. Thus, long-term psychiatric surveillance of these patients and the development of tailored management tools could serve as a means to prevent weight regain.

The Influence of a Roux-en-Y Gastric Bypass on Plasma Concentrations of Antidepressants.

PURPOSE: Roux-en-Y gastric bypass (RYGB) involves alterations of the gastrointestinal tract resulting in altered absorption. Patients with obesity have a higher prevalence of depression, and antidepressants are often prescribed. Alterations caused by RYGB could modify drug bioavailability and cause potential subtherapeutic plasma concentrations, increasing the risk of depressive relapse. The aim of this study was to describe the evolution of trough drug dose-normalized antidepressant plasma concentrations before and after RYGB. MATERIALS AND METHODS: This naturalistic prospective case series considers patients with trough plasma concentrations in a 1-year timeframe before and after RYGB. Only antidepressants prescribed to at least three patients were included in the present study. RESULTS: Thirteen patients (n = 12 females, median age 44 years, median BMI before intervention = 41.3 kg/m2) were included. Two patients were treated concurrently with fluoxetine and trazodone; the remaining patients were all treated with antidepressant monotherapy. Therapeutic drug monitoring (TDM) values for duloxetine (n = 3), escitalopram (n = 4), fluoxetine (n = 4), and trazodone (n = 4) before (median 4.7 weeks) and after (median 21.3 weeks) RYGB intervention were analyzed. Compared to preintervention, median [interquartile range] decreases in dose-normalized trough plasma concentrations for duloxetine (33% [- 47; - 23]), escitalopram (43% [- 51; - 31]), fluoxetine (9% [- 20; 0.2]), and trazodone (16% [- 29; 0.3]) were observed. CONCLUSION: This study shows a decrease in plasma antidepressant concentrations following RYGB. TDM before and after RYGB, in addition to close monitoring of psychiatric symptomatology, may help optimize antidepressant treatment after bariatric surgery. These results also highlight the need for prospective studies assessing the clinical evidence available through TDM in these patients.

[Stigmatization of people with obesity: understanding and confronting societal prejudice]. / Stigmatisation des personnes atteintes d'obésité : comprendre et affronter les préjugés sociétaux.

Obesity (BMI ≥ 30 kg/m2) has been officially classified as a disease by the WHO since 2008, yet individuals affected by obesity often face blame and negative stereotypes from society and healthcare providers. This stigmatization can lead to negative impacts on both mental and physical health. This phenomenon can also lead the stigmatized person to internalize the prejudice, considering their fate as deserved. This article aims to provide healthcare professionals with the tools to better understand and care for patients with obesity.

L'OMS reconnaît officiellement l'obésité (IMC ≥ 30 kg/m2) comme une maladie depuis 2008. Pourtant, les personnes touchées par l'obésité font souvent l'objet de reproches et de stéréotypes négatifs de la part de la société et des prestataires de soins de santé. Cette stigmatisation peut avoir des répercussions négatives sur la santé mentale comme physique. Ce phénomène peut aussi conduire le stigmatisé à intérioriser le préjudice, considérant son sort comme normal. Cet article vise à fournir aux professionnels de santé les outils nécessaires pour comprendre et aborder cette question, afin de mieux soigner les patients touchés par l'obésité.

[GLP-1 and GIP receptor agonists: emerging therapies for obesity]. / Agonistes des récepteurs du GLP-1 et du GIP : des thérapies émergentes de l'obésité.

Obesity is a chronic and recurrent metabolic disease associated with serious complications and increased mortality. Bariatric surgery was until recently the only intervention that could lead to significant and sustained weight loss. A better understanding of the endocrine regulation of appetite has allowed the development of new treatments. GLP-1 analogues are already available and a dual treatment of GLP-1 analogue and GIP has recently shown even greater efficacy in terms of weight loss. We present a summary of the known mechanisms of action and clinical data that support the use of these molecules in the treatment of obesity.

L'obésité est une maladie métabolique chronique et récidivante associée à de graves complications et à une mortalité accrue. La chirurgie bariatrique était jusqu'à récemment la seule intervention permettant d'obtenir une perte de poids significative et son maintien. Une meilleure compréhension de la régulation endocrinienne de l'appétit a permis le développement de nouveaux traitements. Les analogues du GLP-1 sont déjà disponibles et une double activation des récepteurs du GLP-1 et du GIP (double agoniste) a récemment montré une efficacité encore plus importante en termes de perte pondérale. Nous proposons une synthèse des mécanismes d'action connus et des données cliniques qui soutiennent l'utilisation de ces molécules dans le traitement de l'obésité.

[Interdisciplinary Center for Obesity: a single-entry point for personalized care]. / Centre interdisciplinaire de l'obésité : une porte d'entrée unique pour une prise en charge personnalisée.

Obesity is a chronic disease that seriously affects physical and psychological health. However, its management is insufficiently coordinated. The lack of defined therapeutic strategies is particularly evident since the arrival of new drug treatments. Coordination between the professionals involved- obesity specialists, general practitioners and other caregivers - and the involvement of the patient are all issues at the heart of an evaluation necessary for the construction of a personalized care project. Interdisciplinary centers must guarantee access to information and offer the full range of therapies currently available. An early psychological evaluation allows for the orientation of care, taking into account the vulnerability and resources of patients.

L'obésité est une maladie chronique qui affecte gravement la santé physique et psychologique, mais sa prise en charge est insuffisamment coordonnée. L'absence de stratégies thérapeutiques définies est particulièrement évidente depuis l'arrivée de nouveaux traitements médicamenteux. La coordination entre les professionnels impliqués (spécialistes de l'obésité, médecins généralistes et autres soignants) et l'implication du patient sont autant d'enjeux au cœur d'une évaluation nécessaire pour la construction d'un projet de soins personnalisés. Les centres interdisciplinaires doivent garantir un accès à l'information et offrir l'ensemble des thérapies actuellement disponibles. Une évaluation psychologique précoce permet d'orienter la prise en charge en tenant compte de la vulnérabilité et des ressources des patients.

Protein malnutrition after Roux-en-Y gastric bypass: a challenging case and scoping review of the literature.

Although protein malnutrition (PM) is often reported after highly malabsorptive procedures, its exact incidence and mechanisms after Roux-en-Y gastric bypass (RYGB) are poorly understood. The aim of this study was to present a challenging clinical case of PM after RYGB and conduct a scoping review of the literature. Among the 18 studies with 3015 RYGB patients included in the review, the median incidence of PM was 1.7% (range, 0%-8.9%), and it was diagnosed 12 to 120 months after RYGB. The most common cause is insufficient oral intake of protein; however, in cases of persistent hypoalbuminemia, a thorough diagnostic workup needs to be performed. Risk factors for PM after RYGB include specific triggering events such as intractable vomiting and dysphagia, and a total alimentary limb length less than 250 to 300 cm.

Marked weight loss on liraglutide 3.0 mg: Real-life experience of a Swiss cohort with obesity.

OBJECTIVE: This study investigated the effectiveness of liraglutide 3.0 mg daily in combination with a standardized multidisciplinary intervention on body weight and body composition changes in a real-life setting. METHODS: A prospective, observational cohort study design was used. Adult patients with BMI > 35 kg/m2 , or BMI > 28 kg/m2 with greater than or equal to one metabolic comorbidity, were included (n = 54, 65% women). Liraglutide treatment was covered by Swiss health insurance. Clinical and biological data were collected at baseline, 4 months, and 10 months. Body composition was assessed by dual-energy x-ray absorptiometry at baseline and 10 months. RESULTS: At 10 months, mean (SD) percentage weight loss (WL%) was -12.4% (5.5%) or -14.1 (6.6) kg. WL% was ≥5% in 87% of patients at 4 months and in 96% at 10 months. WL% was higher in women (-9.5% [3.1%] vs. men -7.2% [2.5%], p = 0.02) at 4 months and persisted at 10 months (-13.7% [5.2%] vs. -9.6% [5.1%], p = 0.006). WL% was associated with baseline percentage fat mass but not with age or BMI. Body composition showed a decrease in fat mass, visceral adipose tissue, and absolute lean mass. CONCLUSIONS: In a real-world setting, liraglutide 3.0 mg led to beneficial changes in WL and body composition, with a greater impact in women.

Body Composition Assessment by Dual-Energy X-Ray Absorptiometry: A Useful Tool for the Diagnosis of Lipedema.

INTRODUCTION: Lipedema is a poorly known condition. Diagnosis is based almost exclusively on clinical criteria, which may be subjective and not always reliable. This study aimed to investigate regional body composition (BC) by dual-energy X-ray absorptiometry (DXA) in patients with lipedema and healthy controls and to determine cut-off values of fat mass (FM) indices to provide an additional tool for the diagnosis and staging of this condition. METHODS: This study is a single-center case-control study performed at Lausanne University Hospital, Switzerland. Women with clinically diagnosed lipedema underwent regional BC assessment by DXA. The control group without clinical lipedema was matched for age and body mass index (BMI) at a ratio of 1:2 and underwent similar examination. Regional FM (legs, arms, legs and arms, trunk, android and gynoid FM) was measured in (kg) and divided by FM index (FMI) (kg/m2) and total FM (kg). The trunk/legs and android/gynoid ratios were calculated. For all indices of FM distribution showing a significant difference between cases and controls, we defined the receiver operating characteristic (ROC) curves, calculating the area under the curve (AUC), sensitivity, specificity, and Youden's index. Types and stages of lipedema were compared in terms of FM indices. Correlation analyses between all FM distribution indices and lipedema stages were performed. RESULTS: We included 222 women (74 with lipedema and 148 controls). Overall, the mean age was 41 years (standard deviation [SD] 11), and mean BMI was 30.9 kg/m2 (SD 7.6). A statistically significant difference was observed for all DXA-derived indices of FM distribution between groups, except for arm FM indices. The ROC curve analysis of leg FM/total FM, as a potential indicator of lipedema, resulted in an AUC of 0.90 (95% confidence interval 0.86-0.94). According to Youden's index, optimal cut-off value identifying lipedema was 0.384. Sensitivity and specificity were 0.95 and 0.73, respectively. We found no significant differences between lipedema types and stages in terms of FM indices, nor significant correlations between the latter and lipedema stages. DISCUSSION/CONCLUSION: BC assessment by DXA, and particularly calculation of the leg FM/total FM index, is a simple tool that may help clinicians rule out lipedema in doubtful cases.

Increasing prevalence of obesity and diabetes among patients evaluated for liver transplantation in a Swiss tertiary referral center: a 10-year retrospective analysis.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is now the first cause of chronic liver disease in developed countries. We aimed to assess trends in the prevalence of obesity, type 2 diabetes mellitus (T2DM) and NAFLD in patients undergoing liver transplantation evaluation and to assess whether obese patients were less likely to be listed or had an increased drop-out rate after listing. METHODS: We conducted a retrospective study of all consecutive patients who underwent liver transplantation evaluation at a Swiss tertiary referral centre between January 2009 and March 2020. RESULTS: A total of 242 patients were included, 83% were male. The median age was 59 years (IQR, 51-64 years). The most common causes of end-stage liver disease were viral hepatitis (28%), alcoholic liver disease (21%) and NAFLD (12%). Obesity was present in 28% of our cohort, with a significant increase over time. Prevalence of type 2 diabetes mellitus followed the same trend (p = 0.02). The proportions of non-listed and listed obese patients did not differ (21% vs. 30% respectively; p = 0.3). CONCLUSIONS: The prevalence of obesity and type 2 diabetes mellitus significantly increased over our study period. Obese patients had similar chances of being listed. The landscape of liver transplantation indications is shifting towards NAFLD, highlighting the urgent need to prevent NAFLD progression.

[Liraglutide in the treatment of obesity : a multidisciplinary approach]. / Liraglutide dans le traitement de l'obésité : une prise en charge multidisciplinaire.

Liraglutide, which has been prescribed for several years for the treatment of type 2 diabetes, is now proposed for the management of patients with BMI between 28 and 35 kg/m2 in the presence of metabolic comorbidity or BMI ≥ 35 kg/m2. Its reimbursement by the health insurance is conditioned on weight loss results and time limited. Careful preparation of the patient and his commitment to lifestyle changes are essential for the success and good tolerance of the treatment. The introduction of this treatment requires a multidisciplinary follow-up to ensure optimal results. The place of liraglutide in the pharmacopeia of obesity, a chronic disease that requires long-term treatment, should be clarified.

Le liraglutide, un analogue du GLP-1 (Glucagon-Like Peptide-1) prescrit depuis plusieurs années dans le traitement du diabète de type 2, est désormais proposé dans la prise en charge des patients avec un IMC entre 28 et 35 kg/m2 en présence d'une comorbidité métabolique ou avec un IMC ≥ 35 kg/m2. Son remboursement par l'assurance obligatoire des soins est conditionné par des résultats de perte pondérale et limité dans le temps. Une préparation attentive du patient et son engagement dans des modifications de l'hygiène de vie sont indispensables au succès et à la bonne tolérance du traitement. L'instauration de celui-ci nécessite un suivi pluridisciplinaire pour permettre un résultat optimal. La place du liraglutide dans la pharmacopée de l'obésité, maladie chronique qui nécessite un traitement de longue durée, devra être précisée.

[Does liraglutide have a place in psychiatry ?] / Le liraglutide a-t-il sa place en psychiatrie ?

The relative risk of developing MetS is higher in patients with severe mental illness (SMI) than in the general population. Similarly, the risk of developing obesity or type 2 diabetes (T2DM) is also higher in patients with SMI. GLP-1 receptor agonists, such as liraglutide, have been shown to be effective in the treatment of T2DM and, more recently, in obesity or overweight associated with at least one metabolic disease. Their psychiatric adverse effect profiles seem to be reassuring, thus not represent a limitation for prescribing in psy chiatry. We aimed to explore the therapeutic usefulness of liraglutide in patients with psychiatric disorders associated with somatic comorbidities such as obesity, T2DM or MetS.

Le risque relatif de développer un syndrome métabolique (SMet) est plus élevé chez les patients connus pour une maladie psychiatrique sévère (MPS) que dans la population générale. De même, le risque de développer une obésité ou un diabète de type 2 (DT2) est également plus important chez les patients souffrant de MPS. Les analogues du GLP-1 (Glucagon-Like Peptide 1), tels que le liraglutide, ont fait leurs preuves pour le traitement du DT2 et, plus récemment, de l'obésité ou de la surcharge pondérale associée à une maladie métabolique. Leurs profils d'effets indésirables sur la santé mentale semblent rassurants, ne représentant ainsi pas de limitation à leur prescription en psychiatrie. Nous questionnons ici l'intérêt du liraglutide chez les patients souffrant de troubles psychiques associés à des comorbidités somatiques telles que l'obésité, le DT2 ou le SMet.

Body composition and maximal exercise capacity after heart transplantation.

AIMS: Maximal exercise capacity as measured by peak oxygen consumption (pVO2 ) in cardiopulmonary exercise testing (CPET) of heart transplant recipients (HTR) is limited to a 50-70% level of healthy age-matched controls. This study investigated the relationship between body composition and pVO2 during the first decade post-transplant. METHODS AND RESULTS: Body composition was determined by dual-energy X-ray absorptiometry (DXA) and pVO2 by CPET in 48 HTR (n = 38 males; mean age 51 ± 12 years). A total of 95 assessments were acquired 1-9 years post-transplant, and the results of four consecutive periods were compared [Period 1: 1-2 years (n = 25); 2: 3-4 years (n = 23); 3: 5-6 years (n = 23); 4: 7-9 years (n = 24)]. Linear regression analysis analysed the correlation between pVO2 and pairs of appendicular lean mass (ALM) and fat mass (FM). The relation between ALM and daily dose of calcineurin inhibitor (CNI) was explored using partial correlation controlling for age, gender, and height. pVO2 increased from 0.98 (0.34) to 1.35 (0.35) L/min (P < 0.01) between Periods 1 and 4 corresponding to 54.5-63.3% of predicted value. Peak heart rate (HR) raised from 115 ± 19 to 131 ± 23 b.p.m. (P = 0.05), and anaerobic threshold (AT = VO2 achieved at AT) increased from 0.57 (0.18) to 0.83 (0.35) L/min (P < 0.01) between Periods 1 and 3. Median FM normalized to height2 (FMI) always remained elevated (>8.8 kg/m2 ). ALM normalized to body mass index increased from 0.690 (0.188) to 0.848 (0.204) m2 (P = 0.02) between Periods 1 and 4, explaining 45% of the variance of pVO2 (R2  = 0.455; P < 0.001). Eighty-one per cent of the variance of pVO2 (R2  = 0.817; P < 0.001) in multiple regression was explained by AT (ß = 0.488), ALM (ß = 0.396), peak HR (ß = 0.366), and FMI (ß = -0.181). ALM was negatively correlated with daily CNI dose (partial R = -0.258; P = 0.01). CONCLUSIONS: After heart transplantation, the beneficial effect of peripheral skeletal muscle gain on pVO2 is opposed by increased FM. Our findings support lifestyle efforts to fight adiposity and CNI dose reduction in the chronic stable phase to favour positive adaptation of peripheral muscle mass.

Effect of very large body mass loss on energetics, mechanics and efficiency of walking in adults with obesity: mass-driven versus behavioural adaptations.

Understanding the mechanisms involved in the higher energy cost of walking (NCw : the energy expenditure above resting per unit distance) in adults with obesity is pivotal to optimizing the use of walking in weight management programmes. Therefore, this study aimed to investigate the mechanics, energetics and mechanical efficiency of walking after a large body mass loss induced by bariatric surgery in individuals with obesity. Nine adults (39.5 ± 8.6 year; BMI: 42.7 ± 4.6 kg m-2 ) walked at five fixed speeds before (baseline) and after the bariatric surgery (post 1 and post 2). Gas exchanges were measured to obtain NCw . A motion analysis system and instrumented treadmill were combined to assess total mechanical work (Wtot ). Mechanical efficiency (Wtot NCw-1 ) was also calculated. Participants lost 25.7 ± 3.4% of their body mass at post 1 (6.6 months; P < 0.001) and 6.1 ± 4.9% more at post 2 (12 months; P = 0.014). Mass-normalized NCw was similar between baseline and post 1 and decreased at post 2 compared to that at baseline (-6.2 ± 2.7%) and post 1 (-8.1 ± 1.9%; P ≤ 0.007). No difference was found in mass-normalized Wtot during follow-up (P = 0.36). Mechanical efficiency was similar at post 1 and post 2 when compared to that at baseline (P ≥ 0.19), but it was higher (+14.1 ± 4.6%) at post 2 than at post 1 (P = 0.013). These findings showed that after a very large body mass loss, individuals with obesity may reorganize their walking pattern into a gait more similar to that of lean adults, thus decreasing their NCw by making their muscles work more efficiently. KEY POINTS: A higher net (above resting) energy cost of walking (lower gait economy) is observed in adults with obesity compared to lean individuals. Understanding the mechanisms (i.e. mass driven, gait pattern and behavioural changes) involved in this extra cost of walking in adults with obesity is pivotal to optimizing the use of walking to promote daily physical activity and improve health in these individuals. We found that very large weight loss induced by bariatric surgery significantly decreased the energy cost of walking per kg of body mass after 1 year with similar total mechanical work per kg of body mass, resulting in an increased mechanical efficiency of walking. Individuals with obesity may reorganize their walking pattern into a gait more similar to that of adults of normal body mass, thus decreasing their energy cost of walking by making their muscles work more efficiently.