The Lancet Diabetes & Endocrinology Commission proposed a new definition of clinical obesity. We applied clinical obesity in a cohort of Asian patients with metabolic dysfunction-associated steatotic liver disease (MASLD) to evaluate its associations with clinical outcomes. We enrolled 642 MASLD patients with vibration-controlled transient elastography (VCTE) assessment. A subgroup of 254 patients underwent additional bioelectrical impedance analysis (BIA). The diagnosis of clinical obesity required fulfilment of both anthropometric and clinical criteria. At-risk metabolic dysfunction-associated steatohepatitis (MASH) was defined by FibroScan-AST (FAST) score. Major adverse cardiovascular events (MACE) were defined as a composite outcome of acute coronary syndrome or stroke. Among 642 MASLD patients (mean age 55.8 ± 12.5 years; 49.2% male, mean BMI 28.2 ± 4.7 kg/m2, 76% severe steatosis, 12.5% advanced fibrosis/cirrhosis [F3/F4]), 46.1% of patients fulfilled the diagnosis of clinical obesity. Clinical obesity criteria identified more patients with F3/F4 (20.6% vs 8.1%, p < 0.001), severe steatosis (83.8% vs 67.6%, p < 0.001), at-risk MASH (3.4% vs 0%, p = 0.056) and MACE (11.2% vs 2.7%, p = 0.006) compared with BMI-based criteria. Clinical obesity was an independent predictor of F3/F4 (OR 4.074, 95% CI 2.195-7.563, p < 0.001) and severe steatosis (OR 2.441, 95% CI 1.638-3.637, p < 0.001). Among patients with BIA, clinical obesity was associated with a lower appendicular skeletal muscle mass (27.0% vs 41.1%, P < 0.001) and a greater visceral fat index (15 vs 9, p < 0.001) compared with BMI-based criteria. Clinical obesity criteria identified more MASLD patients with F3/F4, severe steatosis, at-risk MASH and MACE compared with BMI-based obesity criteria. It should be regularly utilized for prognostication in MASLD evaluation.
Although obesity is increasingly recognized as a chronic, relapsing disease, clinical consultations remain inconsistently delivered, often perceived by patients as generic, stigmatizing, and insufficiently person-centered. While dissatisfaction with weight-related care is well documented, limited research has systematically examined how patients themselves define the core features of an effective obesity consultation. This study aimed to develop a patient-informed framework for clinical obesity consultations by exploring the expectations and experiences of individuals with lived experience of obesity. A qualitative descriptive design was employed. Twenty adults (BMI ≥ 27 kg/m2 with at least one obesity-related complication) who had received treatment for obesity were recruited via purposive sampling. Semi-structured interviews were conducted via Zoom, transcribed, anonymized, and analyzed using reflexive thematic analysis. Coding was inductive and organized using MAXQDA. Participants articulated a coherent and detailed model of the ideal clinical encounter, extending beyond previously reported dissatisfaction. Five key themes were identified: (1) the need for consent-based and context-sensitive initiation of weight discussions; (2) the rejection of moralizing or reductive language in favor of medically grounded and neutral communication; (3) recognition of obesity as heterogeneous, multifactorial disease requiring individualized assessment; (4) expectations for clear, evidence-based information on treatment options and likely outcomes; and (5) a strong preference for ongoing, relationship-based support rather than episodic advice. Patients revealed that unmet informational and relational needs, especially regarding clinical competence, emotional sensitivity, and collaborative treatment planning, were primary barriers to trust and engagement. This study advances current understanding by proposing a patient-defined model for obesity consultations, with implications for improving clinical communication, shared decision-making, and continuity of care.
Metabolically-dysfunction-associated steatotic liver disease is today rising in prevalence among children and adolescents with obesity. The present Systematic Review and Meta-analysis explores the effect of weight loss interventions, depending on their modality (lifestyle, bariatric surgery or anti-obesity medication) on circulating, imagery-related and histology-related liver parameters in children and adolescents with obesity (aged 5-18 years). After consultation of the main databases (MEDLINE, EMBASE, Web of Science and Google Scholar and the Cochrane Controlled Register of Trials), 145 studies were included, gathering 18609 participants (10539 included in the meta-analysis) allocated to 257 experimental arms (26 diet, 24 medication, 96 multidisciplinary, 39 controls, 16 physical activity, 41 supplementation and 15 surgery). Circulating levels of liver enzymes were found improved in the large majority of the studies (most of them relying on multidisciplinary treatments), with however a lack of positive effect of physical activity programs. Sixty-seven percent of the intervention arms found significant improvements in hepatic fat, with no effect of physical activity interventions according to the meta-analysis. Bariatric Surgery appears as the only modality to improve histology-related parameters. According to the meta-regression, improvements in the Non-alcoholic fatty liver disease Activity Score are associated with the degree of weight loss and Body Mass Index reduction. The present results indicate improved overall liver status in response to weight loss interventions in this population, further studies remain however needed to clarify the effects of physical activity alone. Importantly, results also suggest the necessity to provide adapted and appropriate dietary and multidisciplinary interventions as first line strategies for liver-related health, especially in the context of obesity medication.
Overweight and obesity are associated with insulin resistance. However, the importance of the time of onset of excess body fat is unknown and was presently examined. We included 339 adult participants having information about their body mass index (BMI) at 18 years of age. Insulin action was determined as homeostasis model assessment (HOMA-IR) reflecting liver, hyperinsulinemic euglycemic clamp reflecting skeletal muscle, Adipo-IR reflecting adipose tissue in vivo, and insulin action on lipogeneses reflecting fat cells. The subjects were divided into never having overweight/obesity with BMI always <25 kg/m2 (NO), having BMI ≥ 25 kg/m2 already at 18 years of age (EO), and late onset of overweight when BMI was ≥25 kg/m2 only at current examination (LO). The groups were compared by unpaired t-test and single and multiple regression analysis (the latter to study the influence of other factors than insulin action). EO had 5 kg/m2 higher BMI and was 10 years younger than LO at examination (p < 0.0001). EO was more insulin resistant than LO for both HOMA-IR and Adipo-IR, but not clamp (p = 0.01, 0.02, and 0.11, respectively). However, when the different measures of insulin resistance were corrected for current BMI or age there were no significant differences between EO and LO for any of the measures of insulin action (p ≥ 0.08). Furthermore, in all subjects current BMI (p < 0.0001) but not BMI when 18 years old (p ≥ 0.13) correlated with different insulin resistance measures. When current BMI or age is considered, there is no difference between early or late onset of overweight/obesity for the level of insulin resistance in the different target tissues of the hormone.
Growth hormone not only promotes growth and development via inducing insulin-like growth factor-1 produced by the liver but also regulates glucose and lipid metabolism of peripheral organs, including the liver, adipose tissue, and muscle. Particularly, the relationship between growth hormone and adipose tissue has been recognized since the 1950s. More intensive research focusing on it is emerging, fueled by the new conception that adipose tissue is not merely a passive reservoir for fat storage but a highly active organ with endocrine and metabolic capabilities. As for it, earlier findings have illuminated the effects of growth hormone on adipose tissue, including lipolysis and lipogenesis, adipocyte proliferation and differentiation, adipose cytokine secretion, white fat browning, and adipose tissue fibrosis. Subsequently, recent research has uncovered its involvement in promoting adipose tissue aging, regulating the adipose tissue immune microenvironment, and governing adipocyte subgroup composition. More importantly, decreased serum levels of growth hormone detected in patients with obesity are associated with glucose and lipid metabolism dysfunction. Therefore, this review aims to examine the impact of growth hormone on adipose tissue under the physiological context or pathological contexts based on patients and animal models characterized by either excessive or diminished growth hormone action to indicate a complex interplay of mutual regulatory mechanisms between adipose tissue and growth hormone. Subsequently, the alterations of growth hormone levels in obesity and their implications for glucose-lipid metabolism and adipose tissue have also been reviewed. Therefore, the review will offer novel perspectives on the role of growth hormone in the progression of obesity based on the new conception of adipose tissue and its potential use in therapeutic interventions for obesity.
The impact of GLP-1 receptor agonists (GLP1-RA) treatment on lean mass and body composition in patients with obesity is not fully understood. Systematic review and meta-analysis of RCTs including patients with obesity treated with GLP1-RA at obesity doses, compared with placebo. Search was conducted in PubMed, Embase, and LILACS in March 2025. A meta-analysis was performed using a random-effects model to evaluate the change in lean mass as a proportion of total weight, the absolute and relative changes in lean mass, and adverse effects. Seven studies (821 patients) were included in the analysis. GLP1-RA significantly improved lean mass as a proportion of total weight, with an observed increase of 1.81% (95% CI: 1.1- 2.52; p < 0.00001; I² = 7%). However, a significant decrease was observed in the absolute change in lean mass (-1.74 kg; 95% CI: -3.04 to -0.45; p < 0.00001; I² = 98%) and in the percentage of lean mass (-3.06%; 95% CI: -5.10 to -1.02; p < 0.00001; I² = 98%). Semaglutide demonstrated the most significant reduction in absolute lean mass, with a loss of -5.44 kg (95% CI: -7.07 to -3.81; p < 0.00001). There is an improvement in body composition due to an increase in lean mass as a proportion of total weight, an effect that could be amplified with the use of semaglutide. Our results suggest that lean mass loss should not be considered a limitation for the use of these drugs in patients with obesity. However, it is essential to accompany drug treatment with nutritional and physical exercise interventions to preserve or improve muscle mass and optimize clinical outcomes.
While genetic studies have identified hundreds of loci associated with adiposity, the phenotypic expression of this individual genetic risk is not fixed but dependent on environmental circumstances. Socioeconomic Position (SEP), which includes education, income, and area-level deprivation, serves as an important environmental modulator of genetic liability. However, the literature on Gene-Environment (G×E) interactions remains fragmented, particularly regarding how these evolve across the life course. Provide a comprehensive overview of available literature on how SEP factors relate to the effects of polygenic risk scores (PRS), genetic susceptibility, and epigenetic mechanisms in obesity. Following PRISMA guidelines, we searched five databases for human studies examining SEP, genetic or epigenetic markers, life course, and adiposity-related outcomes. In total, we synthesized 98 studies (79 genetic, 21 epigenetic, including two papers contributing to both domains) and assessed risk of bias using QUIPS. Lower SEP, particularly lower educational attainment and greater area-level deprivation, was often associated with stronger genetic susceptibility to obesity, although findings differed by SEP component, life stage, PRS construction, outcome definition, ancestry, and analytical framework. Among the 29 studies formally testing genetic susceptibility-by-SEP interactions, PRS-size patterns were descriptive rather than indicating a clear hierarchy: large PRS produced the greatest number of formal interaction findings, while medium PRS showed a high proportion of significant findings in fewer and less comparable studies. Epigenetic analyses identified DNA methylation at stress-related and metabolic loci as a potential pathway linking socioeconomic disadvantage to obesity, though tissue specificity and causal direction remain limiting factors. Lower educational attainment and socioeconomic deprivation appear to amplify genetic susceptibility to obesity, although evidence remains heterogeneous in PRS construction, SEP operationalization, outcome definition, ancestry, and analytical framework. Emerging evidence suggests educational attainment and early-life socioeconomic conditions may represent modifiable contexts influencing genetic obesity risk across the life course.
Prior obesity neuroimaging studies used univariate methods and small samples, limiting reproducibility. Employing a large-scale dataset and a two-stage machine learning framework, we identified neuroanatomical signatures of obesity and evaluated their population-level associations with delay discounting impulsivity. We enrolled 243 young adults with obesity and 475 healthy-weight controls from the Human Connectome Project S1200 dataset. Cortical surface area, cortical thickness, and subcortical gray matter volume were extracted using surface-based morphometry. Support vector machine (SVM) classifiers discriminated obesity from healthy weight based on neuroanatomical features, with interpretability assessed via SHapley Additive exPlanations (SHAP). Partial correlations evaluated associations between the 15 SVM-selected features and the area under the curve (AUC) of delay discounting (DD) in the full sample. Normative modeling examined if the obesity group deviated from brain-structure-based expectations of AUC-DD. The neuroanatomical-only SVM achieved a receiver operating characteristic (ROC-AUC) of 0.648; adding demographic and cognitive covariates improved it to 0.740. SHAP highlighted the superior parietal, entorhinal, medial orbitofrontal, posterior cingulate, and rostral anterior cingulate cortices. Ten of the top 15 features were significantly associated with AUC-DD, and all in the expected direction. The obesity group showed systematically higher DD impulsivity than predicted impulsivity by brain structures alone. Distributed neuroanatomical features in prefrontal, medial temporal, cingulate, and parietal cortices discriminated obesity and showed convergent population-level associations with delay discounting impulsivity across group, correlational, and normative analyses.
Overweight is a global health crisis linked to chronic diseases. Traditional indicators like BMI have limitations, whereas novel central obesity indices are superior for assessing obesity-related health risks. We aim to explore the joint association of health-enhancing walking and healthful diet with central obesity. This study utilized data from the 100-Day Walking Program in Bozhou City (2022-2024). Daily step counts were tracked using dedicated pedometers. Central obesity indices, including the waist-to-weight index (WWI), conicity index (C-Index), and body shape index (ABSI), along with body composition parameters, were measured using a body composition analyzer. Linear mixed-effects models and generalized estimating equations were employed to assess the associations of daily steps with the obesity indices and weight loss success, respectively. Among 3 503 participants, the median average daily step count was 12 675. Each 1000-step increment was associated with reductions of 0.014 in WWI, 0.002 in C-Index, and 0.001 in ABSI. Exposure-response curves demonstrated a general decline in these indices with increasing steps. These inverse associations were significantly more pronounced in participants with higher dietary quality scores. In the joint analysis, participants with both higher step counts and higher dietary quality exhibited significantly lower central obesity indices than the reference group with low levels of both. Moreover, each 1000-step increase was associated with a 4% higher probability of successful short-term weight loss. Increasing daily steps is associated with improved central obesity indices and short-term weight loss success, particularly among participants with higher dietary quality.
Obesity is a serious multifactorial disease that involves epigenetic mechanisms like DNA methylation. Tyrosine kinase inhibitors (TKIs), originally synthesized and approved for cancer therapy, have recently been linked to the regulation of obesity. We evaluated whether LPM4870108, a small-molecule TKI with antitumor efficacy, contributes to obesity via DNA methylation. LPM4870108 (TKI) was administered orally to rats at 0, 1.25, 2.5, or 5.0 mg/kg (for 28 days, twice daily). Body weights (BWs) and food intake were recorded daily. After 28 days of administration, ventromedial hypothalamus (VMH) tissues were collected for whole-genome transcriptomic and methylation sequencing to identify candidate genes. The mRNA expression and promoter methylation of candidate genes were analyzed by real-time RT-PCR and pyrosequencing, respectively. Protein levels of DNA methyltransferases (DNMTs) were determined by Western blot. LPM4870108 treatment substantially increased food intake and BW. Whole-genome transcriptomic and methylation profiling identified 415 differentially expressed genes (DEGs) and 124,935 differentially methylated regions (DMRs) within the VMH of LPM4870108-treated rats. The transcriptomic results were combined with whole-genome methylation sequencing data, followed by further verification via RT-PCR and pyrosequencing, through which the obesity-related candidate gene arginine vasopressin (AVP) was identified. Among all DEGs, AVP showed the most prominent change, with a negative association between its promoter methylation and mRNA expression level. Reduced protein expression of DNA methyltransferase 3A (DNMT3A) in the VMH was also detected in LPM4870108-treated rats. These findings indicate that LPM4870108-stimulated hyperphagia and weight gain were associated with DNA hypomethylation and concomitant upregulation of the AVP gene. LPM4870108, tyrosine kinase inhibitors; VMH, ventromedial hypothalamus; RRBS, reduced representation bisulfite sequencing; AVP, arginine vasopressin; DNMT, DNA methyltransferases.
Hypertension is a major public health concern. Although metabolic obesity phenotypes are key risk factors for cardiovascular disease, the association between their dynamic changes and hypertension incidence remains unclear. Based on the Guizhou Population Health Cohort Study (GPHCS), after excluding participants with hypertension at baseline or incomplete data, a total of 3399 subjects were included in the final analysis. Participants were classified into four phenotypes based on body mass index (BMI) and metabolic status: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). Cox proportional hazards models were applied to assess the associations between 16 phenotype transition patterns and the risk of hypertension, with robustness confirmed through multiple sensitivity analyses. Over a median follow-up of 6.42 years, 826 incident cases of hypertension were identified. After multivariable adjustment, compared with MHNW, baseline MHO (HR = 1.26, 95% CI: 1.02-1.55) and MUO (HR = 1.50, 95% CI: 1.22-1.82) were positively associated with hypertension risk, whereas MUNW was not (HR = 1.10, 95% CI: 0.91-1.33). Dynamic analysis showed that 48.75% of participants underwent phenotypic transitions during follow-up. The two most prominent changes were that 37.38% of individuals with MUNW transitioned to MHNW and 31.21% of those with MHO transitioned to MUO. Transitions from any baseline phenotype to MHNW were not associated with a statistically significant increase in hypertension risk (all P > 0.05). All other phenotypic transitions were positively associated. Even participants who remained MHO experienced increased hypertension risk (HR = 2.30, 95% CI: 1.45-3.64). Within the study population, MHO is an unstable state athat tended to progress to MUO, which carries the highest risk of hypertension. In contrast, the MUNW phenotype exhibits high reversibility and can revert to the MHNW phenotype. Future our studies require confirm whether early lifestyle interventions targeting metabolic health can effectively reduce the risk of hypertension.
Obesity is a significant public health issue that has been increasingly linked to various musculoskeletal disorders, including intervertebral disk degeneration (IVDD). The interplay between metabolic dysfunction, chronic inflammation, and biomechanical stress suggests a multifactorial link between obesity and IVDD, warranting further investigation. This review aims to explore the pathophysiological mechanisms through which obesity contributes to IVDD and discuss this relationship's clinical implications. Obesity induces an occurrence of minor chronic inflammation and metabolic abnormalities, which can exacerbate degenerative changes in the intervertebral disks. Pro-inflammatory cytokines (TNF-α and IL-6) secreted by visceral adipose tissue can promote disk degeneration by enhancing catabolic processes and inhibiting anabolic repair mechanisms within the disk matrix. Additionally, mechanical loading due to excess body weight increases stress on the spinal structures, accelerating wear and tear of the intervertebral disks. This review summarizes current research findings on the biochemical and biomechanical pathways linking obesity to IVDD. We examine evidence from epidemiological studies, clinical trials, and animal models that highlight the multifaceted impact of obesity on spinal health. Furthermore, we discuss the implications of these findings for clinical practice, emphasizing the importance of weight management in preventing and treating IVDD. Interventions such as lifestyle modifications, dietary changes, and bariatric surgery are evaluated for their effectiveness in mitigating the adverse effects of obesity on the spine. The review also addresses the potential for targeted pharmacological therapies that modulate inflammatory pathways and mechanical stress responses. Understanding the association between obesity and IVDD is crucial when establishing all-encompassing management approaches for those who are impacted by the growing global prevalence of obesity. By elucidating the pathophysiological underpinnings and clinical consequences of obesity-induced IVDD, this review aims to inform future research directions and clinical guidelines, ultimately improving patient outcomes in this growing population.
The global prevalence of obesity has been steadily increasing, posing major public health challenges. Current universal BMI cut-off points may not accurately reflect obesity risk across different ethnicities, including the Turkish population. This study aimed to evaluate the relationship between body mass index (BMI) and body fat percentage (BF%) and determine appropriate BMI cut-off points for diagnosing obesity in Turkish adults. A cross-sectional study was conducted among Turkish individuals aged 18-65 in four major districts of Kayseri. Anthropometric measurements were obtained, including height, weight, waist circumference, and hip circumference. Body composition was assessed using bioelectrical impedance analysis (BIA). ROC (Receiver Operating Characteristic) curve analysis was performed to identify optimal BMI cut-off points for predicting obesity based on BF%. Pearson correlation analysis evaluated the relationship between BMI and BF%. The participants had a mean age of 39.9 ± 13.3 years, and 51.6% were female. A strong positive correlation between BMI and BF% was found for both women (r = 0.86, p < 0.001) and men (r = 0.68, p < 0.001). The optimal BMI cut-off point for detecting obesity was 28.76 kg/m² for the total sample, 28.80 kg/m² for women, and 28.76 kg/m² for men. Using these new thresholds, the obesity prevalence increased from 27.7% to 33.6%. The AUC values indicated excellent discriminative power for women (AUC = 0.98) and good discriminative power for men (AUC = 0.91). The current universal BMI cut-off points (≥30 kg/m²) may underestimate obesity prevalence in the Turkish population. Establishing national and gender-specific BMI thresholds could improve the accuracy of obesity diagnosis and support more effective public health interventions targeting chronic non-communicable diseases.
The number of children with obesity has risen over the decades, becoming a major public health concern, also because of persistence into adulthood and morbidity. Early-life antibiotic use alters gut microbiota composition, potentially causing metabolic disturbances, increasing the number of children with obesity. To explore the association between early-life antibiotic use and the risk of developing overweight/obesity during childhood, we analyzed data from the Netherlands Twin Register, using a co-twin control design in outcome-discordant pairs to control for confounding due to shared environmental and/or genetic factors. This retrospective study included data from 34,142 twins aged 4.5-15.4 years. Any antibiotic use before age 2 was reported in 24.6% of children; 1.06% were children with obesity, and 9.23% were children with overweight/obesity based on sex- and age-specific BMI thresholds from the International Obesity Task Force and the World Health Organization. We evaluated outcomes for dichotomous and continuous data (BMI Z-scores), adjusting for sex, delivery mode, gestational age, birthweight, breastfeeding, maternal BMI, and parental education levels. No association was found between early-life antibiotic use and the risk of developing obesity (OR 0.82, 95% CI 0.60-1.14) or overweight/obesity (OR 1.00, 95% CI 0.90-1.12) during childhood. Matched co-twin analyses showed similar null results. Also, BMI Z-scores did not differ by antibiotic exposure. These findings suggest that early-life antibiotic use is not associated with an increased risk of overweight or obesity in childhood.
Obesity has become a major global health problem. It is characterized by increased body fat storage and is associated with excessive food intake. Although obesity is often thought of as a simple problem involving fat accumulation in the body, it is a complex disease that alters cellular defense systems and causes low-grade chronic inflammation, which can contribute metabolic syndrome. Even though obesity is an inflammatory disease, an increase in the formation of reactive oxygen species (ROS) is also observed due to excess nutrition. Excessive ROS production contributes to obesity progression and endoplasmic reticulum (ER) stress. In response to oxidative stress, cells activate antioxidant defense mechanisms either through unfolded protein response (UPR) pathways or via UPR-independent signaling pathways. Nuclear factor-erythroid 2-related factor-2 (NRF2) controls the transcription of multiple genes encoding antioxidant and cytoprotective proteins. NRF2 is of interest in obesity research as it can be activated with or without UPR elements and plays a role in the regulation of antioxidant response. Targeting NRF2 through multiple approaches has been shown to reduce or prevent obesity and obesity associated metabolic complications. This review examines the molecular mechanisms of NRF2 activation in obesity, with particular focus on its bidirectional crosstalk with the UPR and discusses the therapeutic implications of targeting this axis in obesity and its related metabolic dysfunction.
There have been recent calls to increase the diagnosis rate of metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we quantified the prevalence of MASLD-associated risk factors and identified individuals at risk of advanced fibrosis in a large, real-world cohort. This was a large, multicenter study of adults attending Dubai Academic Health Corporation between January 2018 and August 2023. MASLD risk factors were defined as the presence of one or more of the following: type 2 diabetes; obesity with ≥1 cardiometabolic risk factor; and/or raised ALT. Fibrosis-4 (FIB-4), a non-invasive index based on age, transaminases, and platelet count, was calculated, with moderate-high risk defined using established cut-offs (≥1.3 for <65 years; ≥2.0 for ≥65 years). Half (n = 46,412, 49.0%) of the population screened at risk of MASLD and, of those, 21.7% were at moderate-high risk of advanced fibrosis. 15.0% of individuals without MASLD risk factors, including those without obesity, were at moderate-high risk of fibrosis. Reliance solely on metabolic risk-based case finding may miss individuals at risk of advanced fibrosis, highlighting the value of broader fibrosis risk assessment strategies.
Obesity is a chronic, relapsing disease that increasingly spans generations within households, yet contemporary metabolic and bariatric surgery (MBS) models remain oriented toward individuals or single-generation patients. A growing body of evidence demonstrates that obesity risk, behaviors, and treatment responses cluster within family systems, and that MBS produces measurable metabolic and behavioral effects among untreated spouses, partners, and children. Concurrently, decades of pediatric research confirm that caregiver engagement and integration is one of the strongest determinants of successful obesity treatment. Together, these observations support a paradigm shift toward an intergenerational, family-centered model of MBS, in which the household becomes the unit of care. This perspective synthesizes evidence supporting the biological, behavioral, and environmental interdependence of obesity within families and outlines a comprehensive framework for implementing household-level bariatric care. Core components include integrated pediatric-adult clinical infrastructure; combined multidisciplinary teams trained across the age spectrum; harmonized protocols for evaluation, education, and follow-up; coordinated scheduling and workflow alignment; and family-based behavioral strategies that promote shared goals, consistent routines, and mutual accountability. Operational and policy innovations, such as cross-departmental agreements, unified electronic health records, and coordinated billing can facilitate sustainable implementation. We further identify research priorities, including quantifying metabolic ripple effects among untreated family members, evaluating bundled household-level interventions, and developing validated metrics to assess changes in the home environment. Treating the household as the patient offers a promising strategy to enhance medical obesity treatment, surgical durability, improve adherence, and disrupt intergenerational transmission of obesity. As obesity increasingly presents as a family condition, an intergenerational MBS model may help realign treatment with the realities of lived experience and improve outcomes across generations.
Accurate identification of comorbidities like Type 2 Diabetes Mellitus (T2DM), Hypertension (HTN), Hyperlipidemia (HLD), and Obstructive Sleep Apnea (OSA) is crucial for managing patients with obesity and for large-scale research. While electronic health record discharge summaries contain rich clinical information, manual extraction is resource-intensive. Large Language Models (LLMs) present a potential automated solution. To evaluate the performance of utilizing LLM in identifying the presence of T2DM, HTN, HLD, and OSA documented within discharge summaries of adult patients with obesity, using administrative ICD codes as the primary reference standard and complete manual review as a secondary sensitivity analysis. This retrospective validation study used MIMIC-IV data. A random sample of 350 discharge summaries was processed by the LLM for the presence or absence of each target comorbidity. Performance was evaluated against ICD-9/10 coding and against manual review of all 350 discharge summaries using accuracy, precision, recall, and F1-score. The analyzed sample included 350 admissions from 341 unique patients (mean age 59.7 [SD 14.3], 60.4% female). Prevalence based on ICD codes was 45.4% for Type 2 Diabetes Mellitus (T2DM), 60.0% for Hypertension (HTN), 55.4% for Hyperlipidemia (HLD), and 29.4% for Obstructive Sleep Apnea (OSA). In the primary ICD-based analysis, F1-scores ranged from 0.815 to 0.948. In the manual-review sensitivity analysis, accuracy was 0.963 for T2DM, 0.971 for HTN, 0.863 for HLD, and 0.966 for OSA, with F1-scores ranging from 0.879 to 0.981. The LLM showed promising concordance with ICD codes for T2DM, HTN, OSA, and HLD in obesity patient discharge summaries. Further research, including validation against clinical expert review and investigation into reasons for discrepancies, is necessary before considering practical applications.
Human endogenous retroviruses (HERVs) are genomic elements derived from ancient retroviral infections and are increasingly recognized for their roles in gene regulation and immune modulation. Obesity is characterized by chronic low-grade inflammation and metabolic dysregulation, which may influence HERV expression. In this study, we evaluated the transcriptional levels of HERV-H-pol, HERV-K-pol, and HERV-W-pol in peripheral blood from adolescents with obesity as compared to healthy normal weight controls (HC). Total RNA was extracted from whole blood samples, and gene expression was assessed using quantitative reverse-transcription PCR (RT-qPCR), with GAPDH as a reference gene. HERV-H-pol and HERV-K-pol were significantly upregulated in adolescents with obesity as compared to HC, whereas HERV-W-pol was downregulated. No significant associations were observed between HERV expression levels and age, sex, or metabolic parameters. These findings suggest that obesity in adolescents is associated with a differential regulation of HERV elements, possibly reflecting the impact of chronic inflammatory and metabolic stress. HERV dysregulation may represent a novel molecular feature of obesity and warrants further investigation as a potential biomarker or contributor to obesity-related complications.
A novel short ACE2 isoform, lacking the SARS-CoV-2 binding domain and upregulated by interferons, was recently identified in human respiratory epithelia, spermatozoa, liver, and gastrointestinal and urogenital tracts. This study is the first to describe its presence in human adipose tissue (AT). AT samples were collected from middle-aged women without obesity in subcutaneous regions-abdominal superficial, abdominal deep, and thigh-as well as from the visceral epiploon. Subcutaneous abdominal AT was also obtained from middle-aged women with previous obesity and from older women with and without obesity. Short ACE2 expression was determined by immunohistochemistry and Western blotting in AT, mature adipocytes, and stromal vascular fraction (SVF). Short ACE2 showed comparable expression in both subcutaneous and visceral AT, with enrichment in adipocytes. In contrast, full-length ACE2 displayed a different pattern, as its levels did not significantly differ between the SVF and adipocytes. Moreover, short ACE2 levels were higher in AT from women with obesity compared with those without obesity. Interestingly, short ACE2 expression was also elevated in AT from women with previous obesity. Given that short ACE2 expression is induced by interferons, its upregulation in AT under obesity may reflect the interferon-enriched inflammatory environment characteristic of this condition. These findings identify AT, particularly adipocytes, as a relevant site for short ACE2 expression and regulation, expanding current knowledge on short ACE2 isoform biology.