International Journal of Obesity最新文献

{"title":"Integrating genetic and transcriptomic data to identify genes underlying obesity risk loci.","authors":"Hanfei Xu, Shreyash Gupta, Ian Dinsmore, Abbey Kollu, Anne Marie Cawley, Mohammad Y Anwar, Hung-Hsin Chen, Lauren E Petty, Sudha Seshadri, Misa Graff, Jennifer E Below, Jennifer A Brody, Geetha Chittoor, Susan P Fisher-Hoch, Nancy L Heard-Costa, Daniel Levy, Honghuang Lin, Ruth J F Loos, Joseph B Mccormick, Jerome I Rotter, Tooraj Mirshahi, Christopher D Still, Anita Destefano, L Adrienne Cupples, Karen L Mohlke, Kari E North, Anne E Justice, Ching-Ti Liu","doi":"10.1038/s41366-025-01898-z","DOIUrl":"10.1038/s41366-025-01898-z","url":null,"abstract":"<p><strong>Background: </strong>Genome-wide association studies (GWAS) have identified numerous body mass index (BMI) loci. However, most underlying mechanisms from risk locus to BMI remain unknown. Leveraging omics data through integrative analyses could provide more comprehensive views of biological pathways on BMI.</p><p><strong>Methods: </strong>We analyzed genotype and blood gene expression data from up to 5619 samples in the Framingham Heart Study (FHS). Using 3992 single-nucleotide polymorphisms (SNPs) at 97 BMI loci and 1408 transcripts within 1 Mb, we performed separate association analyses of transcript with BMI and SNP with transcript (P_BMI and P_SNP, respectively) and then a correlated meta-analysis between the full summary data sets (P_META). Transcripts were prioritized if we identified transcripts that met Bonferroni-corrected significance within each omic, showed stronger associations in the correlated meta-analysis than each omic, and had corresponding SNPs in the SNP-transcript-BMI association that were at least nominally associated with BMI in FHS data. We tested for generalization of identified association in a Hispanic ancestry sample of blood gene expression data and other samples in hypothalamus, nucleus accumbens, liver, and visceral adipose tissue (VAT) with significant threshold: P_META < 0.05 & P_META < P_SNP & P_META < P_BMI.</p><p><strong>Results: </strong>Among 308 significant SNP-transcript-BMI associations, we identified seven genes (NT5C2, GSTM3, SNAPC3, SPNS1, TMEM245, YPEL3, and ZNF646) in five association regions. We generalized results for SNAPC3 and YPEL3 in Hispanic ancestry sample, for YPEL3 in the nucleus accumbens, ZNF646 and GSTM3 in VAT, and NT5C2, SNAPC3, TMEM245, YPEL3, and ZNF646 in liver.</p><p><strong>Conclusion: </strong>The identified genes help link the genetic variation at obesity-risk loci to biological mechanisms and health outcomes, thus translating GWAS findings to function.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145175566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Elucidating pathways to pediatric obesity: a study evaluating obesity polygenic risk scores related to appetitive traits in children.","authors":"Timothy J Renier, Dabin Yeum, Jennifer A Emond, Reina K Lansigan, Grace A Ballarino, Delaina D Carlson, Ruth J F Loos, Diane Gilbert-Diamond","doi":"10.1038/s41366-025-01810-9","DOIUrl":"https://doi.org/10.1038/s41366-025-01810-9","url":null,"abstract":"","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Physiology of the WEight-Reduced State (POWERS) study: environmental, psychological, and social determinants of health.","authors":"Sai Krupa Das, Giada Benasi, John M Jakicic, Wendy C King, Susan Z Yanovski, Stephanie S Kelley, Laurel E S Mayer, Kathryn J Whyte, Michael R Lowe, Susan B Roberts, Maren R Laughlin","doi":"10.1038/s41366-025-01911-5","DOIUrl":"https://doi.org/10.1038/s41366-025-01911-5","url":null,"abstract":"<p><p>Intentional weight loss is often followed by unintentional weight regain. The causes of weight regain are uncertain but may include a myriad of responses that result in increased hunger and decreased energy expenditure. An individual's psychological state and social and physical environments are also thought to influence weight regain in ways that can either support or derail weight loss maintenance. Funded by the National Institutes of Health, the Physiology of the WEight Reduced State (POWERS) study is a multi-center clinical trial aimed at describing the molecular, cellular, physiological, behavioral, environmental and psychosocial factors that may be associated with an individual's ability to maintain their new weight after weight loss. This report provides the rationale for and describes the environmental, psychological and social determinants of health measures used in the POWERS study.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ostracism, cortisol reactivity, and motivation for high-calorie food in children and adolescents with obesity.","authors":"Anna Felnhofer, Andreas Goreis, Lisa Weiss, Helmuth Haslacher, Charlotte Nigmann, Gabriele Skacel, Rodrig Marculescu, Paul L Plener, Susanne Greber-Platzer, Oswald D Kothgassner","doi":"10.1038/s41366-025-01824-3","DOIUrl":"https://doi.org/10.1038/s41366-025-01824-3","url":null,"abstract":"<p><strong>Objective: </strong>Experiencing ostracism (i.e., social exclusion) may impact self-regulatory eating behaviors, particularly in youths with excess weight. Yet, research in pediatric patients with obesity is lacking. Hence, we examined the effect of Virtual Reality(VR)-based ostracism on motivation for food in children and adolescents with BMI ≥97^th percentile.</p><p><strong>Methods: </strong>In a randomized experimental between-subject design, forty-one patients (M_age = 13.37 years, 46% female) with a diagnosis of obesity (ICD-10: E66) were randomized to a social exclusion or inclusion condition in a VR-Cyberball-paradigm. Patients' salivary cortisol, heart rate and heart rate variability were assessed. Furthermore, we measured patients' motivation to consume high-calorie food, their prosocial behavior, their self-reported urge to eat and subjective stress.</p><p><strong>Results: </strong>Results indicate that the experience of social exclusion in youths with obesity leads to a blunted salivary cortisol response; in contrast, no effects of social exclusion on the sympathetic nervous system were observed. Social exclusion was associated with an increased perceived threat to fundamental social needs. Similarly, ostracized participants demonstrated heightened self-regulatory behaviors regarding their motivation for high-calorie food intake, selecting fewer grams of sweets following social exclusion. Furthermore, ostracism tended to increase helping behavior post-exclusion, although this effect was not significant. Self-reported urge to eat and stress levels during the experiment showed no significant effect.</p><p><strong>Conclusion: </strong>Ostracism-induced reduction of motivation for food suggests that affiliative behaviors like increasing compliance regarding eating behaviors may play a role in youths with obesity with BMI ≥97^th percentile in the context of social stress. Future research should explore the broader social context, including family and friends, to better understand the dynamics between social stress, physiological reactivity, and self-regulatory behaviors in treating obesity.</p><p><strong>Clinical trial registration: </strong>As this study does not constitute a clinical trial, the study design and analyses plans were not preregistered.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ototoxic impacts of adipose-derived extracts on a murine auditory cell line: molecular insights from proteomic analyses.","authors":"Appolinaire A Olou, Wesley Tom, Gary Krzyzanowski, Chao Jiang, Dinesh Chandel, Nirmalee Fernando, Rama Thelagathoti, Dominic Cosgrove, M Rohan Fernando","doi":"10.1038/s41366-025-01912-4","DOIUrl":"https://doi.org/10.1038/s41366-025-01912-4","url":null,"abstract":"<p><p>Obesity promotes a range of associated conditions, including hearing impairment; however, mechanisms are lacking. Self-evidently, an insult on any cellular constituent of the auditory organ can disrupt hearing. Here, using the mouse auditory cell line, HEI-OC1, we provide insights into adipose-associated ototoxicity. Adipose extracts from mice with obesity, diet- or genetically induced, suppress HEI-OC1's survival and ATP generation. Proteomic profiling shows an upregulation of the inflammatory response pathway and proteins such as Podoplanin and Low-density lipoprotein receptor. Likewise, the Programmed cell death 4 (PDCD4) protein was induced. These results correspond to a downregulation of glycolysis and oxidative phosphorylation but an upregulation of the G2/M checkpoint. Additionally, pathways such as IL6-JAK-STAT3, IL2-STAT5, interferon gamma response, cholesterol response, bile acid metabolism, RAS, Apoptosis, and TGF-β were upregulated. Furthermore, the adipose extracts cause cellular morphological changes consistent with cells under stress. Functional assays point to alterations in levels of proteins related to calcium and ER homeostasis/stress. The ER-resident protein SARAF, an inhibitor of calcium overfilling, is among the proteins markedly downregulated. GRP78 protein levels increased, suggesting ER/calcium stress. Finally, Thapsigargin impairs HEI-OC1 survival, reminiscent of the effect of the adipose tissue extracts. Our analyses warrant further exploration of inflammation and ER/calcium stress in connection to obesity-associated ototoxicity.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiological associations between obesity, metabolism and disease risk: are body mass index and waist-hip ratio all you need?","authors":"Ville-Petteri Mäkinen, Siyu Zhao, Andrei Ihanus, Tuulia Tynkkynen, Mika Ala-Korpela","doi":"10.1038/s41366-025-01895-2","DOIUrl":"https://doi.org/10.1038/s41366-025-01895-2","url":null,"abstract":"<p><strong>Background/objectives: </strong>Tracking excess adiposity at population scale is essential for managing the obesity pandemic in human populations. New formulas based on weight, height, waist and hip measurements have been suggested as better alternatives to the classic body mass index and waist-hip ratio, but the lack of systematic benchmarking on how these formulas reflect adiposity, metabolic dysfunction and clinical sequelae causes confusion on how to best monitor the health of populations.</p><p><strong>Subjects/methods: </strong>Participants from the Northern Finland Birth Cohort 1966 were included based on data availability at the 46-year visit (2511 women and 1908 men). Cross-sectional sex-adjusted Spearman correlations with clinical biomarkers and serum and urine NMR metabolomics were calculated for body mass index (BMI), waist-hip ratio (WHR), waist-height ratio (WHER), abdominal volume index, body adiposity index, body roundness index, body shape index, conicity index and impedance-based body fat. UK biobank participants were selected based on available data at initial visit (244,947 women and 205,949 men). Prevalent and incident cases of type 2 diabetes, hypertension, liver disease and heart disease were ascertained through register linkage. Prevalent cases were predicted from adiposity measures by age- and sex-adjusted logistic regression and incident cases by age- and sex-adjusted Cox regression.</p><p><strong>Results: </strong>Adiposity measures were highly collinear and exhibited low biomolecular specificity. BMI and WHR together captured almost all body shape information related to cardiometabolic diseases. For instance, the c-statistic of the BMI & WHR model for diabetes (0.8012; CI95: 0.7963, 0.8061) was near the theoretical maximum of 0.8047. Diabetes was also predicted by WHER (0.7951; CI95: 0.7903, 0.8000). Other adiposity measures showed equal or worse prediction accuracy. This pattern repeated across multiple disease diagnoses.</p><p><strong>Conclusions: </strong>We did not observe sufficient benefits from the more recent body adiposity formulas over body mass index, waist-hip or waist-height ratio to warrant their widespread application in cardiometabolic epidemiology.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of obesity on bone health: molecular pathways, metabolic interactions, and associated pathologies.","authors":"Abolfazl Bagherifard, Ahmad Hemmatyar, Karo Khosravi, Ali Rouzbahani, Khatere Mokhtari, Hooman Yahyazedeh, Hamid Tanzadehpanah","doi":"10.1038/s41366-025-01907-1","DOIUrl":"https://doi.org/10.1038/s41366-025-01907-1","url":null,"abstract":"<p><p>Obesity, characterized by excessive body fat accumulation, is a growing global health concern with significant implications for both metabolic and skeletal health. The increasing prevalence of obesity, particularly among children, adolescents, and postmenopausal women, is associated with various bone-related disorders. Obesity and non-alcoholic fatty liver disease (NAFLD) collectively influence bone metabolism through systemic factors such as chronic inflammation, insulin resistance, dyslipidemia, and alterations in adipose tissue function. Key mediators, including adipokines like leptin and adiponectin, along with pro-inflammatory cytokines, play crucial roles in modulating bone formation and resorption, thereby contributing to conditions such as osteopenia and osteoporosis. Moreover, the interplay between obesity, NAFLD, and bone health involves complex mechanisms, including gut microbiota dysbiosis and impaired vitamin D metabolism. Understanding these multifaceted interactions is essential for developing targeted interventions to prevent or mitigate the adverse effects of obesity and NAFLD on bone health. This review explores the molecular pathways, metabolic interactions, and associated pathologies linking obesity and NAFLD to bone health.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic role and mechanisms of vitamins for controlling obesity/adiposity-a brief overview of recent studies.","authors":"Md Hasinur Rahman, Md Ibrahim H Mondal","doi":"10.1038/s41366-025-01908-0","DOIUrl":"https://doi.org/10.1038/s41366-025-01908-0","url":null,"abstract":"<p><p>Obesity/adiposity, an often-intractable disease with serious physical, economic, and societal consequences, is a major problem for health practitioners. Despite extensive research, obesity remains a kind of pandemic. There is significant evidence that individuals with obesity react to both fat-soluble and water-soluble vitamin levels in their serum. Vitamins correlate negatively with body weight, body mass index, and body composition. Certain vitamins may possess anti-adipogenic, anti-inflammatory, and antioxidant properties. Yet still, there is no consensus among researchers about the general impact of vitamins on obesity. A clearer understanding of the effects of vitamins on obesity will make dietary interventions more effective in preventing and treating obesity and its complications. This article analyses the current data about the impact of vitamins on controlling obesity, including their role, action mechanisms and obesity-related metabolic statuses. Such an analysis could enhance our understanding of the effects of vitamins on obesity. So, this article could assist future researchers who are working toward better protocols for treating obesity.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of obesity with musculoskeletal health and functional mobility in females-a systematic review.","authors":"Dhanya Menoth Mohan, Fatme Al Anouti, Nupur Kohli, Kinda Khalaf","doi":"10.1038/s41366-025-01881-8","DOIUrl":"https://doi.org/10.1038/s41366-025-01881-8","url":null,"abstract":"<p><p>Obesity is a prevalent global health challenge with a significant yet unclear impact on musculoskeletal health, particularly among females. This systematic review aimed to unravel the association between obesity and musculoskeletal health, as well as functional mobility in women. A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and the Cochrane Library for articles published between January 2001 and December 2023. Studies were selected based on their examination of the relationship between overweight or obesity and musculoskeletal health (including bones, joints, and soft tissues) and/or functional mobility in adult females (age ≥19) within the general population. Studies focusing on selective populations, or involving subjects with other health conditions or work-related musculoskeletal issues, were excluded. The data collected revealed a direct impact of obesity on musculoskeletal health, gait, and functional mobility, especially among women. Markedly, there was a strong association between obesity and musculoskeletal pain, particularly lower back pain. Obesity significantly alters gait biomechanics, leading to increased plantar pressure, altered kinematic patterns, and higher energy expenditure during walking. Higher BMI was found to significantly impact mobility-related limitations. Data also revealed that obesity, especially with BMI levels above 35 kg/m², adversely affects weight-bearing tasks such as walking, stair climbing, and chair rise ability. The findings of this systematic review emphasize the need for targeted interventions to address obesity-related mobility challenges, gait alterations and musculoskeletal pain to allow independence and enhanced functional outcomes in the daily activities of individuals with obesity. Exploring gender differences in obesity towards better understanding of the effect of obesity on the musculoskeletal health and functional mobility of women is critical for devising female-specific mitigation measures and optimizing management and treatment modalities, including pharmacotherapy.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Body mass index and the risk of ulnar nerve entrapment in individuals without diabetes-a longitudinal cohort study from Sweden.","authors":"Mattias Rydberg, Lars B Dahlin, Peter M Nilsson, Malin Zimmerman","doi":"10.1038/s41366-025-01899-y","DOIUrl":"https://doi.org/10.1038/s41366-025-01899-y","url":null,"abstract":"<p><strong>Introduction: </strong>Ulnar nerve entrapment (UNE) is a common disorder with many associated risk factors. Diabetes mellitus (DM) is an established risk factor, but less is known about metabolic risk factors in individuals without diabetes. Our study aimed to explore the association of body mass index (BMI) with UNE during long-term follow-up.</p><p><strong>Method: </strong>The population-based cohort study Malmö Diet and Cancer Study (MDCS) and the Swedish Patient Register (NPR) were cross-linked. Between 1991 and 1996, 30,446 subjects were recruited to MDCS and were followed to a diagnosis of UNE, emigration, death, or end of study on December 31, 2020. BMI at study entry was stratified into normal weight (<25), overweight (25-30) and obesity (>30). To omit the effect of DM, individuals with prevalent or incident DM were excluded. To calculate the association between BMI and incident UNE, Cox proportional hazard models adjusted for age, sex, hypertension, smoking, manual work, and alcohol consumption were used.</p><p><strong>Results: </strong>A total of 23,254 individuals were followed for over 25 years, whereof 192 (0.8%) developed UNE. In the multivariable Cox regression models, BMI was independently associated with UNE (HR 1.07; 95% CI 1.03-1.11, p < 0.001). Both overweight (HR 1.55; 95% CI 1.12-2.15, p < 0.01) and obesity (HR 2.23; 95% CI 1.40-3.57, p = 0.001) were associated with an increased risk compared to individuals with normal weight.</p><p><strong>Conclusion: </strong>High BMI is associated with the development of UNE in individuals without diabetes, indicating that high BMI is an independent risk factor for the development of nerve entrapment disorders irrespective of hyperglycaemia.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}