International Journal Of Obesity (2005)[JOURNAL]
Sun
200 papers
Novel perspectives on PPARγ regulation: from SPPARMs to the emerging role of lncRNAs in metabolic disorders.
Qin H, Wang Y, Yang Y … +4 more , Xiong Y, Luo L, Peng L, Zhang L
Int J Obes (Lond) · 2026 Jun · PMID 42310385 · Publisher ↗
Metabolic disorders-particularly obesity and type 2 diabetes mellitus (T2DM)-have reached pandemic proportions and represent one of the most pressing global health challenges of the 21st century. Peroxisome proliferator-...
Metabolic disorders-particularly obesity and type 2 diabetes mellitus (T2DM)-have reached pandemic proportions and represent one of the most pressing global health challenges of the 21st century. Peroxisome proliferator-activated receptor gamma (PPARγ) serves as a master regulator of lipid metabolism, insulin sensitivity, and adipocyte differentiation, making it a validated therapeutic target. However, classical thiazolidinediones (TZDs) targeting PPARγ are limited by significant adverse effects including weight gain, fluid retention, and cardiovascular risks. This review systematically examines the structure-function relationships of PPARγ and its multi-layered regulatory mechanisms in metabolic homeostasis. We particularly focus on selective PPARγ modulators (SPPARMs) that target Ser273 phosphorylation-a strategy that preserves insulin-sensitizing efficacy while circumventing TZD-associated toxicities. Notably, we provide the first comprehensive integration of the lncRNA Snhg9 into the PPARγ regulatory framework; the Snhg9-CCAR2-SIRT1-PPARγ axis represents a novel lncRNA-mediated mechanism with potential implications for RNA-based therapeutics. Finally, we propose the DNA-binding domain (DBD) as an emerging target that may enable gene-selective PPARγ modulation-a paradigm shift beyond conventional ligand-binding domain (LBD)-focused strategies. This review provides a strategic roadmap for next-generation PPARγ-targeted therapies in metabolic diseases.
Metabolism-disrupting compounds and metabolic health during the menopausal transition: a narrative review.
Guetterman HM, Flaws JA, Strakovsky RS
Int J Obes (Lond) · 2026 Jun · PMID 42298107 · Publisher ↗
Substantial evidence has linked endocrine-disrupting chemicals and other compounds to increased risk of elevated adiposity and adverse metabolic outcomes. Individuals may be particularly susceptible to these metabolism-d...
Substantial evidence has linked endocrine-disrupting chemicals and other compounds to increased risk of elevated adiposity and adverse metabolic outcomes. Individuals may be particularly susceptible to these metabolism-disrupting chemicals or compounds (MDC) during sensitive periods. The menopausal transition is a sensitive window marked by increased risk of obesity, metabolic syndrome, and cardiovascular disease that continues into the postmenopausal period; however, evidence on modifiable risk factors, such as MDC exposure, in perimenopausal individuals is limited. Therefore, we conducted a review to understand the breadth of literature evaluating relationships of MDC exposure with metabolic health outcomes (e.g. body weight/composition, glycemic control, lipid profiles, blood pressure) across the menopausal transition. We identified 28 studies using data from four U.S.-based cohorts of midlife women. Overall, studies suggest that phthalates and other nonpersistent chemicals (7 studies), per- and polyfluoroalkyl substances (7 studies), persistent organic pollutants (3 studies), heavy metals (5 studies), and air pollutants (6 studies) were associated with increases in body fat, unfavorable adipokine profiles, adverse lipid profiles, and/or higher risk of type 2 diabetes and hypertension. Several studies identified differences by race/ethnicity. Although few studies stratified by menopause status, some results suggest that perimenopause may be a sensitive window of exposure to MDCs. Additional data are needed to identify susceptible windows of exposure during midlife, particularly in more diverse populations. Future research should consider examining cumulative exposure to multi-pollutant mixtures and identifying susceptible populations and mitigation strategies during this period.
Association between immune-inflammatory biomarkers (NLR, PLR, SII, SIRI) and obesity in adults: a systematic review and meta-analysis.
Yang Y, Wang J, Cai J … +7 more , He X, Wang N, Zheng M, You J, Yao Z, Yang H, He Y
Int J Obes (Lond) · 2026 Jun · PMID 42288649 · Publisher ↗
BACKGROUND: Obesity is regarded as a chronic, low-grade systemic inflammatory condition. However, whether immune-inflammatory indices derived from routine peripheral blood tests-including the neutrophil-to-lymphocyte rat...
BACKGROUND: Obesity is regarded as a chronic, low-grade systemic inflammatory condition. However, whether immune-inflammatory indices derived from routine peripheral blood tests-including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI)-can accurately reflect obesity-associated inflammation remains controversial, as existing studies have reported inconsistent findings. Comparing these indices between people with obesity and people without obesity, and further evaluating sources of heterogeneity and their potential clinical implications, is of considerable significance for clarifying their role in obesity research and clinical application. METHODS: Relevant studies published up to September 30, 2025, were systematically searched in PubMed, EMBASE, the Cochrane Library, and Web of Science databases. A meta-analysis was conducted using standardized mean differences (SMDs) to evaluate overall effects, with additional subgroup and sensitivity analyses performed (PROSPERO registration number: CRD420251247523). RESULTS: A total of 30 studies were included, comprising 94,408 people with obesity and 129,927 people without obesity as controls. The meta-analysis demonstrated that NLR (SMD = 0.46, 95% CI: 0.10-0.82, p < 0.001), SII (SMD = 2.45, 95% CI: 0.89- 4.01, p < 0.001), and SIRI (SMD = 0.84, 95% CI: 0.47-1.22, p < 0.001) were significantly higher in the group of people with obesity compared with controls, whereas PLR showed no statistically significant difference (SMD = 0.00, 95% CI: -0.08-0.09, p > 0.05). Subgroup analyses indicated that these associations were more prominent in studies defining obesity by BMI, among individuals with chronic comorbidities, and within Asian and American populations. CONCLUSION: NLR, SII, and SIRI may serve as potential low-cost biomarkers reflecting systemic inflammation associated with obesity, while PLR appears to have limited applicability. Future high-quality prospective studies are needed to validate their clinical utility in obesity risk stratification, prediction of complications, and monitoring of therapeutic responses, as well as to explore the potential value of combining these indices with traditional inflammatory and metabolic biomarkers.
Genetic and environmental influences on educational disparities in adult weight change: an individual-based pooled analysis of 11 twin cohorts.
Obeso A, Drouard G, Jelenkovic A … +36 more , Medda E, Fagnani C, Toccaceli V, Latvala A, Aaltonen S, Medland SE, Gordon SD, Lee J, Lee SJ, Sung J, Pyun H, Duncan GE, Buchwald D, Ordoñana JR, Sánchez-Romera JF, Carrillo E, Franz CE, Kremen WS, Corley RP, Huibregtse BM, Magnusson PK, Karlsson IK, Dahl Aslan AK, Lyons MJ, Bartels M, Ligthart L, de Geus EJC, Gatz M, Butler DA, Pool R, Eriksson A, Bruins S, Martin NG, Boomsma DI, Kaprio J, Silventoinen K
Int J Obes (Lond) · 2026 Jun · PMID 42286115 · Publisher ↗
INTRODUCTION: Educational attainment (EA) is negatively associated with body mass index (BMI), but less is known about the association between EA and adult BMI change. We analysed the role of genetic and environmental fa...
INTRODUCTION: Educational attainment (EA) is negatively associated with body mass index (BMI), but less is known about the association between EA and adult BMI change. We analysed the role of genetic and environmental factors in the associations between EA and BMI trajectory components over adulthood. DATA AND METHODS: Pooled data from 59,490 twins aged 31-99 years (49% women) across 11 cohorts with EA and repeated measures of BMI were used. BMI trajectory components (baseline BMI and BMI change per decade) were estimated using linear mixed-effects (LME) and delta slope methods. EA was derived by regressing years of education on birth year and cohort. Associations between EA and BMI trajectories were evaluated with LME models in both cohort-specific and pooled data. Genetic and environmental contributions were evaluated using structural equation modelling. RESULTS: EA was more strongly negatively associated with baseline BMI and BMI change (mean of 1.31 and 1.32 kg/m per decade in men and women, respectively) in women (β = -0.14 kg/m², 95% CI: -0.15 to -0.12; β = -0.02 kg/m²/decade, 95% CI: -0.03 to -0.01, respectively) than in men (β = -0.07, 95% CI: -0.08 to -0.06; β = -0.01, 95% CI: -0.02 to -0.001, respectively). The associations between baseline BMI and EA were explained by genetic factors in men (r = -0.10) and by both genetic (r = -0.17) and unique environmental factors (r = -0.07) in women. For BMI change, the associations with EA were explained by genetic factors (r = -0.04 in men; -0.06 in women). CONCLUSION: Individuals with higher EA tend to have lower baseline BMI and slower BMI increases across adulthood. These associations are primarily genetically mediated.
Capturing infant and child growth dynamics with P-splines mixed effects models.
Hernandez MA, Li Z, Cole TJ … +3 more , Ong YY, Tilling K, Elhakeem A
Int J Obes (Lond) · 2026 Jun · PMID 42286114 · Publisher ↗
BACKGROUND: Investigating early life growth dynamics is important for understanding the developmental origins of obesity. Basis splines (B-splines) provide excellent flexibility for modelling complex growth patterns, but...
BACKGROUND: Investigating early life growth dynamics is important for understanding the developmental origins of obesity. Basis splines (B-splines) provide excellent flexibility for modelling complex growth patterns, but they are prone to overfitting. Penalised B-splines (P-splines) extend B-splines by using a penalty to control their flexibility and avoid overfitting. Despite their advantages, P-splines remain underused in epidemiology, partly due to lack of guidance and accessible software. Our aim was to provide a guide on applying P-spline linear mixed effects models to analyse early life growth trajectories and extract key growth features. METHODS: We outline the theoretical foundation and fitting procedures for P-splines and illustrate their use on repeated height, weight, and body mass index (BMI) measures up to age 10 years from a Southeast Asian birth cohort (n = 1014). P-splines linear mixed effects models were fitted by reformulating P-splines as mixed models with sparse matrices for efficient estimation. From the fitted trajectories, we estimated infant peak growth velocity, magnitude and timing of infant peak BMI and childhood rebound BMI, and examined their sex differences, intercorrelations, and associations with prenatal factors. RESULTS: Infant peak height velocity (means:.4.4 vs. 3.9 cm/month) and peak weight velocity (1121 vs. 890 grams/month) was higher in boys than girls. Infancy peak BMI (17.4 vs. 16.8 kg/m), childhood rebound BMI (15.1 vs. 14.9 kg/m), age at peak BMI (5.8 vs. 6.4 months), and age at rebound BMI (5.4 years) were comparable between sexes. Ages of peak and rebound BMI had a negligible correlation, higher maternal height was associated with higher peak growth velocity, higher maternal early-pregnancy weight was associated with higher and earlier rebound BMI, and higher birth weight was associated with higher and earlier peak BMI. CONCLUSIONS: P-splines simplify knot selection, making them a valuable approach for growth modelling. Software, code and datasets are provided to promote uptake of this method.
Dual amylin and calcitonin receptor agonists as multifaceted disease-modifying osteoarthritis drugs.
Mohamed KE, Larsen AT, Thudium CS … +4 more , Bezerra A, Karsdal MA, Bay-Jensen AC, Henriksen K
Int J Obes (Lond) · 2026 Jun · PMID 42265185 · Publisher ↗
Obesity is a powerful driver in the development and progression of osteoarthritis (OA), contributing to increased mechanical load and metabolic stress, making it a valuable target for treatment. Weight loss is a cornerst...
Obesity is a powerful driver in the development and progression of osteoarthritis (OA), contributing to increased mechanical load and metabolic stress, making it a valuable target for treatment. Weight loss is a cornerstone of OA management, improving patients' quality of life and disease outcomes. This review examines the potential of dual amylin and calcitonin receptor agonists (DACRAs) as disease-modifying osteoarthritis drugs. We highlighted the relevant pathophysiological pathways of metabolically driven OA, previously studied pharmacotherapies, and clinical and preclinical evidence demonstrating that DACRAs target multiple OA pathways. Among the investigated pharmacotherapies, there have been no extensive evaluations of weight-loss drugs for OA. More potent weight-loss pharmacotherapies have been tested in clinical trials for the treatment of OA in recent years. However, not all weight-loss pharmacotherapies possess the qualities essential for OA management. DACRAs are notable for their multifaceted effects on OA management. DACRAs induce weight loss by activating the amylin receptor, thereby improving patients' quality of life and reducing OA pain intensity. Additionally, DACRAs activate the calcitonin receptor, known for its skeletal pain-relieving effects and for slowing down bone remodeling, potentially preserving the joint's cartilage and bone. With their dual action on metabolic and skeletal pathways, DACRAs offer a unique combination of weight loss, pain relief, and a positive influence on joint structures, distinguishing them from other weight-loss pharmacotherapies and making them a worthy candidate for further investigation in osteoarthritis, particularly when driven by metabolic dysfunction.
Triglyceride-glucose index trajectories and the incident risk of type 2 diabetes mellitus in Chinese adults with normal weight: the China-PAR project.
Wu Y, Zhao Y, Zhang Y … +14 more , Gu M, Liang J, Su Y, Chen T, Yang L, Wen L, Huo W, Fu X, Guo B, Li J, Lu X, Hu F, Hu D, Zhang M
Int J Obes (Lond) · 2026 Jun · PMID 42249133 · Publisher ↗
OBJECTIVE: The association between the longitudinal trajectory changes of triglyceride-glucose (TyG) index and type 2 diabetes mellitus (T2DM) is still unclear among the population with normal weight; hence, we aimed to...
OBJECTIVE: The association between the longitudinal trajectory changes of triglyceride-glucose (TyG) index and type 2 diabetes mellitus (T2DM) is still unclear among the population with normal weight; hence, we aimed to identify the trajectories of TyG index and to explore their association with T2DM in the Chinese population with normal weight. METHODS: We included 21,373 participants with normal weight who participated in at least 3 surveys in the project entitled Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR Project). Latent mixture modeling was used to identify the distinct trajectories. The associations between TyG index trajectories and the incident risk of T2DM were examined using the logistic regression model. RESULTS: We identified five TyG index trajectories: low-increasing (28.01%), moderate-increasing (53.93%), moderate high-increasing (14.81%), high-U shape (1.09%), and high-increasing (2.16%). During the mean 12.9 years of follow-up, 1215 participants developed T2DM. After adjusting for confounders, the odds ratio (OR) and 95% confidence interval (CI) of T2DM were 3.00 (2.41-3.76) for the moderate-increasing group, 8.19 (6.43-10.51) for the moderate high-increasing group, 8.42 (5.27-13.17) for the high-U shape group, and 17.39 (12.53-24.17) for the high-increasing group, when compared with participants in the low-increasing group. The sex-specific trajectories and their association with the incident risk of T2DM were similar to those in the total population. The associations remained robust with sensitivity analysis and subgroup analysis. CONCLUSION: Among the Chinese population with normal weight, those with a high-increasing TyG index trajectory may face a higher risk of T2DM compared with those with a low-increasing trajectory. Persistently lower TyG levels are associated with a reduced risk of T2DM in the normal-weight population.
A mental model of obesity: comparing expert and public perceptions in Ireland, the UK, and the US.
Robertson DA, Andersson Y, Lavin C … +1 more , Lunn PD
Int J Obes (Lond) · 2026 Jun · PMID 42249132 · Publisher ↗
OBJECTIVE: Despite scientific evidence on the environmental causes of obesity, policies that target these causes frequently face public opposition. This study investigates the mental model that the public hold about obes...
OBJECTIVE: Despite scientific evidence on the environmental causes of obesity, policies that target these causes frequently face public opposition. This study investigates the mental model that the public hold about obesity, including perceptions of the causes, consequences and responsibility for obesity, alongside support for different preventive policies. METHODS: N = 2400 members of the public undertook a cross-sectional online survey across 3 English-speaking countries with high obesity rates: Ireland, the UK and the US. We benchmarked public perceptions against N = 51 experts. RESULTS: We found differences between countries and larger differences between the public and expert samples. The public assigned considerable blame and responsibility to individuals, while the expert sample focused more on societal and environmental causes. Although the public and expert samples concurred on the seriousness of the problem, the latter endorsed more radical policies, such as taxes and restrictions. CONCLUSIONS: Public health communications often focus on highlighting obesity as a public health problem, but our findings suggest that this message has been received. Instead, more work may be needed to challenge public beliefs about the causes of, and responsibility for, the obesity epidemic.
Exercise reprograms the gut microbiota to enhance metabolic outcomes after bariatric surgery: a translational, cross-species study.
Lima AP, Novais JB, Antunes AEC … +18 more , Calgaro M, Merege-Filho C, Rezende DN, Romero MA, Santo André HC, Baptista I, de Sá Pinto AL, de Cleva R, Santo MA, Dantas WS, Gil S, Rodrigues MRC, Artioli GG, Vitulo N, Roschel H, Gualano B, Nicoletti CF, Benatti FB
Int J Obes (Lond) · 2026 Jun · PMID 42243519 · Publisher ↗
BACKGROUND/OBJECTIVES: Exercise training has been associated with metabolic improvements in bariatric patients beyond weight and fat loss, potentially involving modulation of the gut microbiota. We investigated whether e...
BACKGROUND/OBJECTIVES: Exercise training has been associated with metabolic improvements in bariatric patients beyond weight and fat loss, potentially involving modulation of the gut microbiota. We investigated whether exercise-related microbial changes are associated with metabolic adaptations in women undergoing Roux-en-Y gastric bypass (RYGB) by combining a randomized controlled exercise intervention trial in women post-surgery with a human-to-mouse fecal microbiota transplantation (FMT) experiment. SUBJECTS/METHODS: Thirty-two women were randomized to RYGB (n = 16) or RYGB plus a 6-month exercise training program initiated three months post-surgery (RYGB + ET; n = 16), while a lean control group (LEAN; n = 16) was evaluated at baseline. Blood and fecal samples were collected before surgery, and at 3 (POST3) and 9 (POST9) months following surgery for biochemical, inflammatory, and microbiota analyses. RESULTS: Both surgical groups showed comparable improvements in body composition and inflammation; however, RYGB + ET was associated with greater improvements in HDL, triglycerides, fasting glucose, and fasting insulin. Exercise was also associated with increased gut microbiota α-diversity and shifts in microbial composition, including enrichment of genera previously linked to short-chain fatty acid (SCFA) metabolism and host metabolic health. To explore the potential contribution of these microbial communities, fecal microbiota collected at POST9 were transplanted into 36 high-fat diet-fed female mice, generating recipient groups rRYGB, rRYGB+ET, and rLEAN. Mice receiving RYGB + ET microbiota displayed similar inflammatory status and glucose tolerance, but lower fasting insulin and HOMA-IR, along with partial preservation of intestinal morphology, compared with mice receiving RYGB microbiota. CONCLUSIONS: These findings suggest that exercise following bariatric surgery is associated with distinct gut microbial configurations and metabolic improvements, and that exercise-conditioned microbiota may contribute to aspects of host metabolic regulation after surgery.
Long-term effect of sweeteners and sweetness enhancers on gene expression markers of adipose tissue function, adipocyte morphology, and metabolic health: a SWEET substudy.
Pang MD, Bastings JJAJ, Jocken JWE … +8 more , Harrold JA, Halford JCG, Kjølbæk L, Raben A, Adam TCM, Blaak EE, Goossens GH, SWEET consortium
Int J Obes (Lond) · 2026 Jun · PMID 42230988 · Publisher ↗
BACKGROUND/OBJECTIVES: We investigated the effects of sweeteners and sweetness enhancers (S&SEs) in replacement of sugar on gene expression markers of adipose tissue (AT) function, adipocyte morphology, and metabolic hea...
BACKGROUND/OBJECTIVES: We investigated the effects of sweeteners and sweetness enhancers (S&SEs) in replacement of sugar on gene expression markers of adipose tissue (AT) function, adipocyte morphology, and metabolic health in adults during weight maintenance (WM) following weight loss (WL). SUBJECTS/METHODS: As part of a randomized controlled trial (European SWEET-project), 83 adults were enrolled in the study, which consists of a dietary intervention, comprising a 2-month WL-phase and a 10-month WM-phase during which participants followed a healthy diet (<10E%-added sugar) with (S&SEs group) or without S&SEs (sugar group). At baseline, after WL, and at the end of WM, we determined body composition, whole-body/tissue-specific insulin sensitivity (oral glucose tolerance test), abdominal subcutaneous adipocyte size and AT gene expression. RESULTS: WL decreased adipocyte size and improved insulin sensitivity (both P < 0.001), which was accompanied by a significant downregulation of genes involved in adipogenesis (CEBPɑ, P = 0.004), fatty acid uptake (LPL and SREBF1, both P < 0.001), fatty acid synthesis (FASN and SCD, both P < 0.001), intracellular lipolysis (ATGL, P < 0.001; HSL, P = 0.001), leptin (LEP, P < 0.001), and mitochondrial function (CS, P = 0.048) in AT. The S&SEs-group tended to regain less weight than the sugar group during the WM-phase (3.0 ± 1.2 vs. 5.9 ± 1.0 kg, respectively; P = 0.050). During the WM-phase, the S&SEs group showed a less pronounced increase in AT LPL gene expression (P = 0.041), while ABHD5 expression decreased compared to the sugar group (P = 0.036). No group differences in adipocyte size, expression of genes involved adipogenesis/oxidative metabolism/inflammation, the sweet taste receptor TAS1R3 and insulin sensitivity were found. CONCLUSIONS: S&SE-intake during a 10-month WM-phase following WL altered AT gene expression of lipolytic markers, without affecting adipocyte morphology and insulin sensitivity in adults with overweight/obesity. TRIAL REGISTRATION: ClinicalTrials.gov NCT04226911, Sweeteners and Sweetness Enhancers: Prolonged Effects on Health, Obesity and Safety (SWEET).
Exercise attenuates obesity-related cognitive and sleep-circadian dysfunctions by attenuating neuroinflammation via JAK/STAT in sex and age specific manner.
Yadav A, Barkley M, Watson JC … +3 more , Patel D, Pickering AM, Melkani GC
Int J Obes (Lond) · 2026 Jun · PMID 42230987 · Publisher ↗
BACKGROUND: Obesity including genetic obesity accelerates age-related cognitive decline and disrupts circadian regulation, increasing the risk of neurodegenerative disorders. These effects are mediated in part by metabol...
BACKGROUND: Obesity including genetic obesity accelerates age-related cognitive decline and disrupts circadian regulation, increasing the risk of neurodegenerative disorders. These effects are mediated in part by metabolic dysregulation, neuroinflammation, and altered sleep-circadian cycles, yet the molecular and lifestyle factors that modify obesity-associated brain dysfunction remain poorly defined. OBJECTIVES: We investigated whether exercise mitigates metabolic, cognitive, and circadian dysfunction associated with genetic obesity, and whether exercise responses differ by sex and age. METHODS: Using Drosophila melanogaster (fruit fly), we compared Canton-S (CS) controls with flies carrying a loss-of-function mutation in sphingosine kinase 2 (Sk2), a conserved regulator of sphingolipid metabolism linked to obesity. Male and female flies were assessed at 3 and 6 weeks of age under exercised and non-exercised conditions. Outcomes included brain and peripheral lipid accumulation, synaptic marker expression, neuroinflammatory and apoptotic gene expression, sleep-circadian architecture, and olfactory aversive learning. RESULTS: Flies with Sk2-associated obesity exhibited increased lipid accumulation, synaptic dysregulation, neuroinflammation, sleep fragmentation, and cognitive impairment, with severity increasing with age. Endurance exercise significantly attenuated these abnormalities, but responses were sex- and age-dependent. Exercise reduced brain lipid burden and synapsin expression predominantly in males, whereas females showed greater suppression of inflammatory and apoptotic signaling. Sleep continuity and circadian stability improved markedly with exercise in females, while cognitive performance was rescued in both sexes, with stronger effects at younger ages. CONCLUSIONS: Endurance exercise mitigates obesity-associated metabolic, inflammatory, circadian, and cognitive dysfunction in a genetic Drosophila model, with distinct sex- and age-specific patterns of benefit. These findings highlight exercise as a powerful, non-pharmacological modifier of obesity-related brain aging/inflammation and underscore the importance of considering biological sex and intervention timing when designing strategies to promote healthy aging.
Dietary intake of polybrominated diphenyl ethers (PBDEs) and the risk of obesity in the French E3N cohort.
Ren X, Frenoy P, Artaud F … +5 more , Marques C, Severi G, Nicolas G, Huybrechts I, Mancini FR
Int J Obes (Lond) · 2026 Jun · PMID 42230986 · Publisher ↗
BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants, with the primary exposure pathway for the general population being the consumption of contaminated food. Human exposure to PBDEs is su...
BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants, with the primary exposure pathway for the general population being the consumption of contaminated food. Human exposure to PBDEs is suspected to increase the risk of obesity. OBJECTIVES: This study aims to investigate the association between intake of PBDEs and the risk of obesity/overweight or weight gain in the French Etude Epidémiologique auprès des femmes de l'Education Nationale (E3N) cohort. METHODS: This study included 66 467 women with a mean age of 52.47 years over a 20-years follow-up. Cox proportional hazard regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between PBDEs intake and risk of obesity, overweight and gain more than 10 kg. RESULTS: Higher PBDEs intakes were related to increased risk of overweight (HR (1-SD increment) = 1.07 (1.05-1.09), HR (Q4 vs. Q1) = 1.13 (1.07-1.19), P-trend <0.001) and weight gain (HR (1-SD increment) = 1.12 (1.09-1.14), HR (Q4vsQ1) = 1.28 (1.21-1.37), P-trend <0.001). A non-linear association (P-non-linearity = 0.0014, P-overall <0.001) between the intake of PBDEs and obesity risk (HR (Q4 vs. Q1) = 1.25 (1.15-1.37), P-trend <0.001) was identified. The associations remained consistent when adjusting in addition separately for total fat, polyunsaturated fatty acids (PUFA), n-3 PUFA, the main food sources of PBDEs intake as well as when running stratified analyses based on the follow-up duration. CONCLUSIONS: This study identified a positive association between intake of PBDEs and the risk of overweight, obesity and weight gain. Further efforts are needed to reduce PBDEs contamination in food and lower exposure levels in the general population.
Altered hypothalamic functional connectivity in adolescents with severe obesity.
Shapiro ALB, Pauley ME, Moore JM … +8 more , Hall L, Stence N, Johnson SL, Nadeau KJ, Keller KL, Rolls BJ, Cornier MA, Tregellas JR
Int J Obes (Lond) · 2026 Jun · PMID 42230985 · Publisher ↗
BACKGROUND/OBJECTIVES: Neurobiological frameworks of obesity in youth have focused largely on non-homeostatic systems (reward, salience, executive control), while the homeostatic system-particularly the hypothalamus-is c...
BACKGROUND/OBJECTIVES: Neurobiological frameworks of obesity in youth have focused largely on non-homeostatic systems (reward, salience, executive control), while the homeostatic system-particularly the hypothalamus-is comparatively understudied. A clearer picture of how these systems interact in adolescents with severe obesity is needed to inform treatment. This study sought to test whether adolescents with severe obesity exhibit altered hypothalamic functional connectivity, relative to healthy-weight peers, across fasting and fed states. SUBJECTS/METHODS: We analyzed data from the Food and Adolescent Brain Study, a single-blinded randomized cross-over trial (NCT04208256) of 13-18-year-old adolescents with severe obesity (SO; body mass index [BMI] >99th %ile; n = 30; mean [SD] age 14.6 years [1.5]) and with healthy weight (HW; BMI <85th %ile; n = 26; 15.5 years [1.6]). INTERVENTIONS/METHODS: Participants completed resting-state functional magnetic resonance scans during fasting and after ingesting a 75-gram glucose drink (1 255.8 kJ [300 kcal]) to induce a fed state. Multivariate general linear models were run in seed-to-voxel analyses to estimate functional connectivity, setting the hypothalamus as the seed region. All models were adjusted for sex and household income with significance determined via cluster-forming voxel-level p < 0.005 and false discovery rate-corrected cluster-level p < 0.05. RESULTS: In adolescents with SO, during fasting, hypothalamic connectivity was weaker to the bilateral cerebellum and left(L) middle occipital gyrus, and stronger to the right(R) postcentral/supramarginal gyri, compared to the HW group. During the fed state, hypothalamic connectivity increased to the bilateral middle frontal gyri and R putamen and decreased to the R caudate and L superior frontal gyrus in adolescents with SO, relative to the HW group. CONCLUSION: Severe obesity in adolescence is associated with altered communication between homeostatic (hypothalamus) and non-homeostatic brain structures, evident across fasting and fed states. Findings underscore the need to incorporate homeostatic circuitry into pediatric obesity frameworks.
Associations of body composition and resting metabolic rate with homeostatic and hedonic components of appetite.
Alruwaili A, Trotman H, Haenebalcke L … +12 more , Chuen ASJ, Partington M, Roberts B, Engin B, Malaikah S, Hopkins M, Finlayson G, Sanders J, Thackray AE, Stensel DJ, Willis SA, King JA
Int J Obes (Lond) · 2026 Jun · PMID 42230984 · Publisher ↗
BACKGROUND: While fat-free mass (FFM), fat mass (FM), and resting metabolic rate (RMR) influence energy intake, their specific roles as homoeostatic and hedonic drivers of eating-and factors moderating these relationship...
BACKGROUND: While fat-free mass (FFM), fat mass (FM), and resting metabolic rate (RMR) influence energy intake, their specific roles as homoeostatic and hedonic drivers of eating-and factors moderating these relationships-are uncertain. This study examined associations of FFM, FM, and RMR with a comprehensive set of appetite-related outcomes in adults. METHODS: 130 participants (58% male; age: 25.0 ± 8.5 years; BMI: 24.0 ± 3.7 kg/m²; mean ± SD) completed assessments of RMR (indirect-calorimetry), body composition (air-displacement plethysmography), energy intake (laboratory-based), appetite-related hormones (fasted and meal-stimulated), appetite (visual analogue scales), food reward (Leeds Food Preference Questionnaire [LFPQ]), food cravings (Control of Eating Questionnaire), taste and smell perception. GLM examined associations between exposure and outcome variables, controlling for demographic and lifestyle factors. Effect modification was assessed via interaction terms and stratified analyses with median splits for continuous variables. RESULTS: RMR was positively associated with energy intake (P < 0.001), while FFM and FM were not. The positive RMR-energy intake association was stronger in individuals who were younger, more active, smokers, and with lower BMI (P ≤ 0.020). FFM was positively associated with postprandial peptide-YY (PYY) and hunger, craving control and smell sensitivity (P ≤ 0.026). FM was positively associated with fasting PYY and leptin, and inversely associated with postprandial PYY and hunger, craving control, and taste sensitivity (P ≤ 0.047). RMR was inversely associated with fasting ghrelin (P < 0.001). No consistent associations were observed between body composition, RMR and food reward (LFPQ). Several associations were moderated by age, sex, BMI, physical activity and smoking. CONCLUSIONS: RMR is a key driver of energy intake, with sex, BMI, physical activity and smoking status moderating the relationship. Body composition (FFM and FM) is linked to distinct variations in homoeostatic and hedonic components of appetite, particularly gut hormone responses, craving control and taste perception.
Artificial intelligence in cardio-kidney-metabolic care: Transforming integrated disease management through data-informed innovation.
Young CF, MacLeod J
Int J Obes (Lond) · 2026 Jun · PMID 42225950 · Publisher ↗
Artificial intelligence (AI) is rapidly transforming the landscape of chronic medical conditions, such as cardio-kidney-metabolic (CKM) issues linked to type 2 diabetes and obesity. It creates new opportunities to shift...
Artificial intelligence (AI) is rapidly transforming the landscape of chronic medical conditions, such as cardio-kidney-metabolic (CKM) issues linked to type 2 diabetes and obesity. It creates new opportunities to shift from reactive to proactive, data-driven care. Recent advances include predictive algorithms for hypoglycemia and hyperglycemia, decision-support tools for insulin titration, and generative and agentic AI applications that can enhance patient engagement, streamline clinical workflows, and provide personalized education. For individuals with chronic conditions, AI-powered technologies offer hope in reducing disease burden, supporting self-management, and improving quality of life. For clinicians, AI offers opportunities to analyze and interpret large amounts of glucose, medication, and behavioral data, thus supporting personalized care and freeing more time to focus on psychosocial and lifestyle factors. Despite these benefits, challenges remain, such as ensuring equitable access, integrating AI into primary care, building trust among clinicians and patients, and addressing ethical issues related to data use. This review will synthesize current evidence on AI's impact on diabetes and CKM care and education, highlight opportunities for interdisciplinary teams to utilize AI tools, and outline future directions for research and clinical practice. By examining AI's potential and limitations, this article aims to equip clinicians with the knowledge needed to adopt AI-enabled approaches to better manage chronic diseases.
The impact of adjuvant anti-obesity medications on 10-year weight loss outcomes after sleeve gastrectomy.
Hornick MA, Duffy AJ, Floch NR … +1 more , Morton JM
Int J Obes (Lond) · 2026 May · PMID 42225949 · Publisher ↗
INTRODUCTION: Few studies have documented 10-year outcomes after sleeve gastrectomy (SG) in patients in the United States (US). This single-institution retrospective study reviewed longitudinal weight loss in young patie...
INTRODUCTION: Few studies have documented 10-year outcomes after sleeve gastrectomy (SG) in patients in the United States (US). This single-institution retrospective study reviewed longitudinal weight loss in young patients who underwent SG more than 10 years ago and followed their adjuvant use of semaglutide and tirzepatide. We hypothesized that adjuvant AOM use would be associated with better long-term weight outcomes. METHODS: We retrospectively reviewed records of all adult patients at our institution who underwent SG before 45 years old between January 2013 and December 2014. Patients were required to have BMI data available at least 9.5 years after SG, and those who underwent conversion to gastric bypass (RYGB) were excluded. Longitudinal weight loss outcomes were compared between patients taking semaglutide and/or tirzepatide for at least 1 year at the most recent documented visit and patients not taking adjuvant AOMs at the most recent visit. RESULTS: 111 patients met the criteria for inclusion. There were 67 patients not taking adjuvant AOMs and 44 patients taking adjuvant AOMs at the most recent visit (semaglutide in 29 patients and tirzepatide in 15 patients). In patients not taking adjuvant AOMs, the mean percent total weight loss (%TWL) was 14.1% at mean 10.6 years after SG. In patients taking adjuvant AOMs, mean %TWL was 25.7% at mean 10.7 years after SG (p < 0.001). On average, patients started AOMs 7.6 years after SG and had been taking AOMs for 3.0 years at the time of most recent visit. Groups had similar weight loss trajectories prior to initiation of adjuvant medications. CONCLUSION: Among younger patients who underwent SG at our institution more than 10 years ago, patients currently taking adjuvant semaglutide and/or tirzepatide demonstrated significantly better long-term weight loss than patients not taking adjuvant AOMs. This study suggests that adjuvant AOMs can optimize long-term weight outcomes after SG, even when started many years postoperatively.
Correction: Weight-related changes in MRI-derived measures of body composition and liver steatosis: a large-scale analysis for obesity trial design.
Nowak M, Núñez L, Pagliaro T … +7 more , Robson MD, Duncker C, Kaplan LM, Heymsfield SB, Thomaides Brears H, Bell JD, Thomas EL
Int J Obes (Lond) · 2026 May · PMID 42215766 · Full text
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A gender-sensitized lifestyle intervention powered by sport fandom in men with overweight or obesity: a 1-year cost-effectiveness analysis of the Hockey FIT Trial.
Marsh JD, Silva NCBS, Gill DP … +5 more , Riggin B, Zou G, Stranges S, Zwarenstein M, Petrella RJ
Int J Obes (Lond) · 2026 May · PMID 42209661 · Publisher ↗
BACKGROUND/OBJECTIVES: To describe the program-related costs and estimate the cost-effectiveness of Hockey Fans In Training (Hockey FIT), a gender-sensitized lifestyle intervention, over a 1-year period. SUBJECTS/METHODS...
BACKGROUND/OBJECTIVES: To describe the program-related costs and estimate the cost-effectiveness of Hockey Fans In Training (Hockey FIT), a gender-sensitized lifestyle intervention, over a 1-year period. SUBJECTS/METHODS: We conducted a pragmatic, cluster randomized trial among men aged 35-65 years with a body mass index ≥27 kg/m, in 39 community-based Canadian sites, allocated to either Hockey FIT or a wait-list control group. We estimated the cost-effectiveness of Hockey FIT in terms of both weight loss and quality adjusted life years (QALY) from both a healthcare payer and societal perspective. RESULTS: There were 657 participants included in this analysis (360 control; 297 Hockey FIT). Baseline characteristics were similar between groups. The total intervention cost was $6832.20 CAD per site or $341.61 CAD per participant. The total mean cost for participants in the Hockey FIT group over the 12-month study period were slightly greater than the control group from the healthcare payer perspective (mean difference = $72.94 CAD; 95% CI: $531.17-$677.06, corresponding to a percentage difference of +7.4%) and from the societal perspective (mean difference = $395.31 CAD; 95% CI: -$1247.40-$2038.02, percentage difference of +13.2%), however differences were not statistically significant. Participants in the Hockey FIT group had significantly greater weight loss at 12 months compared to the control group (mean difference = 1.51 kg (95% CI: -2.42- -0.59) resulting in an incremental cost of $48.30 CAD per kilogram weight loss from the healthcare payer perspective, and $261.79 CAD per kilogram weight loss from the societal perspective. There were no significant differences in quality adjusted life years, resulting in incremental ratios of $36,470 CAD/QALY gained (payer) and $197,655 CAD/QALY (societal). CONCLUSION: A lifestyle intervention that engaged men through the power of sport fandom (Hockey FIT) resulted in greater weight loss, with minimal additional costs, and no significant differences in healthcare resource use over one year in middle-aged men with overweight or obesity.
Gut microbiota alteration contributes to bone marrow mesenchymal stem cells connexin43 response to high-fat diet induced obesity in mice.
Ning K, Chen Y, Yang X … +5 more , Dou X, Liu S, Wang DE, Niu Y, Xu H
Int J Obes (Lond) · 2026 May · PMID 42203970 · Publisher ↗
BACKGROUND/ OBJECTIVE: Bone marrow mesenchymal stem cells (BMSCs) contribute to controlling adipose tissue homeostasis and may be a potential target for obesity therapy. Since lack of connexin43(Cx43) in mesenchymal stem...
BACKGROUND/ OBJECTIVE: Bone marrow mesenchymal stem cells (BMSCs) contribute to controlling adipose tissue homeostasis and may be a potential target for obesity therapy. Since lack of connexin43(Cx43) in mesenchymal stem cells (MSCs) is known to combat high-fat diet (HFD)-induced adiposity. Also, HFD is a well-known risk factor for gut microbiota dysbiosis. Here we attempt to address the interaction between HFD, gut microbiota, and Cx43 deficiency in BMSCs during the development of obesity. METHODS: BMSC-specific Cx43 knockout (Prrx1-Cre;Cx43(cKO)) and control littermate (Cx43(flox))mice were fed a regular chow diet or a HFD for 8 weeks. Cecal microbiome composition was assessed by 16S ribosomal RNA (rRNA) sequencing, and further analyzing correlation between gut microbiota and obesogenic parameters. Moreover, transplantation fecal microbiota was used to probe the salutary effect of BMSC Cx43. RESULTS: HFD fed cKO mice notably altered cecal microbiome composition as proved by a distinctively clustered separation from flox mice. Concomitantly, Allobaculum induced by HFD was strongly correlated positively with body weight, glucose intolerance, and adipose mass. The recipients with gut microbiota from cKO mice displayed anti-obesity phenotype as the donors. CONCLUSIONS: Gut microbiota alteration may be one main reason for the salutary effect of BMSC Cx43 knockout on body adiposity.
SGLT2 inhibitors are associated with reductions in epicardial adipose tissue volume and thickness: a meta-analysis.
Khanna S, Kalman E, Thungathurthi K … +7 more , Thakur U, Vasanthakumar S, Virk S, Bhat A, Lin A, Arnott C, Nerlekar N
Int J Obes (Lond) · 2026 May · PMID 42191874 · Publisher ↗
BACKGROUND: Epicardial adipose tissue (EAT), a metabolically active fat depot surrounding the myocardium, is implicated in the pathogenesis of cardiovascular disease. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) h...
BACKGROUND: Epicardial adipose tissue (EAT), a metabolically active fat depot surrounding the myocardium, is implicated in the pathogenesis of cardiovascular disease. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have demonstrated cardioprotective effects beyond glucose lowering, including a modification of EAT. We performed a systematic review and meta-analysis to evaluate the effect of SGLT2i on serial EAT measurement. METHODS: A comprehensive search of PubMed, Medline, EMBASE, Cochrane Library and grey literature (English only, 2000-2025) was performed for studies assessing EAT pre- and post-SGLT2i treatment, or SGLT2i vs conventional therapy, using computed tomography, echocardiography, or cardiac magnetic resonance. Data were meta-analysed using random-effects models with standardised mean differences (SMD) as summary effects. RESULTS: A total of 11 studies, including 284 patients, were included (89 with echocardiographic EAT thickness assessment and 195 with volumetric measurement using CT or CMR). In analyses comparing SGLT2 inhibitors with conventional antidiabetic therapy, treatment was associated with a significant reduction in EAT (Hedges g - 1.64, 95% CI -2.10 to -1.18; p < 0.01). In exploratory within-group analyses, SGLT2 inhibitor therapy was associated with a reduction in EAT from baseline to follow-up (Hedges g - 0.62, 95% CI -0.88 to -0.36; p < 0.01). On modality-specific subgroup analysis, reductions were observed in both EAT thickness (echocardiography) (Hedges g - 0.74, 95% CI -1.05 to -0.43; p < 0.01) and EAT volume (CT/CMR) (Hedges g - 0.54, 95% CI -0.90 to -0.18; p < 0.01), with no significant difference between modalities (p = 0.32 for interaction). SGLT2 inhibitor therapy was also associated with modest reductions in body mass index (Hedges g - 0.23, 95% CI -0.43 to -0.03; p = 0.03) and systolic blood pressure (Hedges g - 0.32, 95% CI -0.59 to -0.05; p = 0.02). Exploratory subgroup analyses suggested larger reductions in EAT in studies evaluating dapagliflozin compared with empagliflozin; however, this indirect comparison was based on a small number of heterogeneous studies and should be considered hypothesis-generating only. CONCLUSIONS: SGLT2i significantly reduces EAT volume and thickness, which may contribute to their broad cardiovascular benefits. Targeting EAT may represent a novel therapeutic approach for mitigating cardio-metabolic risk. STUDY REGISTRATION: PROSPERO CRD42024621242 SGLT2 inhibitor therapy is associated with reduced epicardial adipose tissue (EAT) across multimodality imaging (Hedges g -0.62), with consistent effects on both thickness and volume. Modest reductions in body mass index and systolic blood pressure were also observed, alongside improvements in inflammatory and metabolic markers.
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