Nutrition & Metabolism最新文献

{"title":"Obesity is the culprit behind fatty acid-induced inflammation.","authors":"Yahui Guo, Haodi Luan, Jing Lin","doi":"10.1186/s12986-026-01076-6","DOIUrl":"10.1186/s12986-026-01076-6","url":null,"abstract":"<p><p>The global prevalence of obesity has emerged as one of the most severe public health challenges of the 21st century. Research conducted over the past decade has fundamentally transformed our understanding of the pathological essence of obesity. Rather than being viewed as a static state of energy accumulation, it is now regarded as a driver of chronic low-grade inflammation. Within this inflammatory process, the composition of dietary fatty acids and metabolic dysregulation plays central roles. The considerable imbalance in the omega-6/omega-3 polyunsaturated fatty acid ratio within contemporary dietary structures, in conjunction with elevated saturated fatty acid intake, collectively establishes the metabolic foundation of the inflammatory microenvironment. This paper provides a systematic review of recent research advances, revealing how obesity reshapes the fatty acid metabolism profile, activates multi-organ inflammatory networks, and ultimately forms a vicious cycle of “obesity-fatty acids-inflammation.” This field has seen breakthrough discoveries ranging from gut microbiota-host interactions to immune cell metabolic reprogramming and from adipose tissue endocrine dysfunction to neuroinflammation. These discoveries have not only deepened our understanding of the mechanisms underlying obesity-related complications but also provided novel perspectives for developing precision anti-inflammatory strategies targeting fatty acid metabolism.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ashwagandha (Withania Somnifera): a comprehensive narrative review of its role in enhancing physical performance and health.","authors":"Hadi Nobari, Nazila Parnian-Khajehdizaj, Kelly Johnson, Juan José Ramos-Álvarez","doi":"10.1186/s12986-026-01093-5","DOIUrl":"10.1186/s12986-026-01093-5","url":null,"abstract":"<p><p>Ashwagandha (Withania somnifera), commonly known as Indian ginseng or winter cherry, is a prominent adaptogenic herb recognized for its profound impact on physical performance and health. As an adaptogen, Ashwagandha stands out for its unique ability to restore system functions to normal, enhance the body’s resilience to stress, and elevate overall performance. This comprehensive narrative Review underscores the diverse health benefits of Ashwagandha, emphasizing its roles in immunomodulation, stress reduction, antioxidant effects, cardioprotection, anti-inflammatory, anti-tumor, and anti-cancer activities, neuroprotection, memory enhancement, cognitive function, physical performance, and sexual health improvement effects. With a rich phytochemical profile, including alkaloids and withanolides like Withaferin A, Ashwagandha showcases efficacy in mitigating stress-related markers, improving sleep quality, and regulating mitochondrial function. In addition to its anticancer potential against various types of cancer, Ashwagandha improves lipid profile and protects the heart from necrosis. Also, Ashwagandha has physical performance benefits, which indicate its potential to increase muscle strength, facilitate muscle regeneration, and improve cardiorespiratory endurance. This narrative review delves into the most recent findings and provides a comprehensive overview of the current understanding of Ashwagandha’s potential uses and effects on physical performance and health.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13032348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146227766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Middle-aged and older populations with different subtypes and definitions of metabolic syndrome face different future cardiovascular disease risks: results from a comparison of two Chinese definitions.","authors":"Hong Yang, Yunda Huang, Guihua Jiang, Hang Guo, Zhiping Duan","doi":"10.1186/s12986-026-01095-3","DOIUrl":"10.1186/s12986-026-01095-3","url":null,"abstract":"<p><p>BACKGROUND: Differences in the association between metabolic syndrome (MetS) and cardiovascular disease (CVD) across definitions and subtypes are unknown. The aim of this study was to investigate the differences between the associations of MetS defined by the Chinese Diabetes Society (CDS) and the Writing Group of 2024 Chinese Guidelines for the Management of Hypertension (WCGH) with CVD. METHODS: This cohort study included participants aged ≥ 40 years without cardiovascular disease from the 2011 survey of the China Health and Retirement Longitudinal Study. Individuals meeting different definitions of MetS based on criteria from the CDS and the WCGH were identified and followed up until 2020. Cox proportional risk models were used to analyze the association between different definitions and subtypes of MetS with CVD, and the predictive performance of the models was compared using the area under the curve (AUC) of the time-dependent receiver operating characteristic curve, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). RESULTS: Both CDS and WCGH based MetS were significantly associated with increased CVD risk, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.51 (1.38 ~ 1.66) and 1.81 (1.66 ~ 1.99), respectively, both P < 0.001. 7 of the 16 subtypes of MetS based on CDS were not associated with CVD; all 5 subtypes of MetS based on WCGH were significantly associated with an increased risk of CVD. When participants were grouped based on meeting two definitions, compared with the CDS-WCGH- group, CVD risk increased most significantly in the CDS-WCGH + group (HR and 95%CI: 2.57 [1.94 ~ 3.39], P < 0.001), showed a significant increase in the CDS + WCGH + group (HR and 95%CI: 1.66 [1.51 ~ 1.83], P < 0.001), and showed no significant increase in the CDS + WCGH- group (HR and 95%CI: 0.93 [0.7 ~ 1.23], P = 0.606). The AUC of WCGH was higher than that of CDS at all time points. IDI and NRI analyses showed that the WCGH standard demonstrated significant improvements in risk reclassification and identification compared to CDS. CONCLUSIONS: The association between MetS and CVD depends on the definition criteria and specific component combinations employed. The WCGH definition, which integrates diagnostic criteria for dyslipidemia, has been demonstrated to be more robust than the CDS. </p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13020297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum 25(OH)D concentration and risk of all-cause and cause-specific mortality in patients with chronic kidney disease: systematic review and dose-response meta-analysis of observational cohort studies.","authors":"Sonya Karimi Hacheso, Sina Naghshi, Sevil Kiani, Halimeh Amirazad, Naimeh Mesri Alamdari, Nazila Farrin, Neda Lotfi Yagin, Amir Bahrami, Helda Tutunchi, Farzad Najafipour","doi":"10.1186/s12986-026-01089-1","DOIUrl":"10.1186/s12986-026-01089-1","url":null,"abstract":"<p><p>BACKGROUND: To summarize the evidence on the associations between 25-hydroxyvitamin D (25(OH)D) and risk of mortality in patients with chronic kidney disease (CKD). METHODS: A comprehensive search of PubMed, Scopus, Web of Science, and Google Scholar for relevant papers published up to November 2025 that assessed the association between serum vitamin D levels and the risk of all-cause, cardiovascular disease (CVD), non-CVD, and cancer mortality was conducted. The lowest-versus-highest analysis and the linear and non-linear dose-response analyses were performed using a random-effects model. RESULTS: Overall, 36 publications (35 studies) with a total sample size of 129,135 participants, aged between 18 and 90 years, were included in the current meta-analysis. During the follow-up periods ranging between 3 months and 18 years, 117,403 cases of all-cause mortality, 2,568 cases of CVD mortality, 886 cases of non-CVD mortality, and 289 cases of cancer mortality were identified. The summary relative risk (RR) and 95% confidence intervals (CIs) comparing lowest versus highest levels of 25(OH)D was 1.61 (95% CI: 1.41–1.84, I2 = 89%, n = 28 studies, very low certainty) for all-cause mortality, 1.68 (95% CI: 1.41-2.00, I2 = 20%, n = 9, very low certainty) for CVD mortality, 1.33 (95% CI: 0.94–1.89, I2 = 26%, n = 3, very low certainty) for non-CVD mortality, and 1.51 (95% CI: 1.09–2.09, I2 = 26%, n = 1, very low certainty) for cancer mortality. There was evidence of non-linearity in the analysis of all-cause and CVD mortality, with a greater reduction in risk from serum levels of 12.5 nmol/L up to 60 nmol/L compared to higher levels, but with slight further reductions in risk with serum levels up to 110 nmol/L. CONCLUSIONS: This meta-analysis provides further evidence that lower levels of 25(OH)D are associated with a higher risk of all-cause, CVD, and cancer mortality in CKD patients. However, all outcomes were graded as very low certainty, and the observed associations may be influenced by confounding, small-study effects, and wide prediction intervals that include the null. Observed low-risk range around ~ 60 nmol/L in the non-linear dose-response analyses, should be interpreted cautiously and requires validation in randomized controlled trials. REGISTRATION: The protocol for this review was registered in PROSPERO (2025 CRD42025105350). </p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13020290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal relationship between obesity, leptin, and brain structure and functional connectivity: evidence based on bidirectional and mediation mendelian randomisation analyses.","authors":"Yue Wu, Fuyuan Deng, Man Bai, Guangpeng Zhang, Ziyuan Li, Mengmeng Wen, Jing Zhang, Runhua Li, Yanmin Shi, Liming Lu, Xinguang Xiao","doi":"10.1186/s12986-026-01081-9","DOIUrl":"10.1186/s12986-026-01081-9","url":null,"abstract":"<p><p>This study used Mendelian randomisation (MR) to explore the putative causal relationship between obesity, leptin, brain alternations represented by magnetic resonance imaging (MRI) phenotypes, and Mediation MR to confirm the mediating role of leptin in obesity and brain changes. The fusiform surface area (SA) (pFDR = 0.005), the bankssts SA (pFDR = 0.022), and the second principal components for fractional anisotropy (FA PC) in posterior thalamic radiation (pFDR = 0.042) had negative causal effects on obesity. Obesity risk had negative causal effects on the first FA PC in superior frontal-occipital fasciculus (pFDR = 0.020) and mean fractional anisotropy (FA) of superior frontal-occipital fasciculus (pFDR = 0.020). Leptin content was positively associated with the risk of obesity (pFDR = 0.020). The inferior parietal SA was negatively correlated with leptin content (p = 0.022). Leptin may serve as a potential mediator of obesity-induced shrinkage of the inferior parietal SA (95% CI = -0.012 to 1.111; p = 0.049). This study supports the potential bidirectional causal relationship between obesity and several aspects of brain macro- and microstructure and functional connectivity (FC), and leptin may be involved in the causal pathway from obesity to brain alterations.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific in the nonlinear associations of hemoglobin glycation index and all-cause mortality in the general US adult population: results from NHANES 1999-2018.","authors":"Chaolan Wang, Ke Lin, Hong Zhang, Tianbao Liu, Zhen Zeng, Wanpei Luo, Yan Jiang, Xiang Zhang, Shuang Du","doi":"10.1186/s12986-026-01088-2","DOIUrl":"10.1186/s12986-026-01088-2","url":null,"abstract":"<p><strong>Background: </strong>The hemoglobin glycation index (HGI) and its association with mortality risk in the United States adults remain insufficiently understood. This research explores potential links between HGI levels and all-cause mortality using nationally representative data.</p><p><strong>Methods: </strong>>The relationship between HGI and mortality was investigated using data from National Health and Nutrition Examination Survey (NHANES) (1999-2018) covering 19,287 U.S. adults. HGI was calculated via linear regression of glycated hemoglobin A1c (HbA1c) on fasting plasma glucose (FPG). The National Death Index was utilized to link mortality outcomes, with tracking continuing through December 31, 2019. To explore sex-specific associations, we utilized weighted Cox regression models with multivariable adjustments, along with restricted cubic splines and segmented Cox analyses. Robustness was confirmed through stratified analyses and sensitivity tests.</p><p><strong>Results: </strong>In U.S. males, HGI showed a U-shaped association with mortality (threshold: -0.131). Below this, lower HGI was protective (hazard ratio (HR) 0.52; 95% confidence interval (CI) 0.42-0.66); above it, higher HGI increased risk (HR 1.34; 95% CI 1.16-1.55). In females, an L-shaped pattern emerged, where higher HGI below the threshold correlated with a decreased likelihood of mortality (HR 0.48; 95% CI 0.40-0.59). These sex-specific associations were verified through stratified and sensitivity analyses.</p><p><strong>Conclusions: </strong>The cohort study observed a U-shaped pattern between HGI and all-cause mortality in U.S. males, whereas an L-shaped association was found in females. These sex-specific patterns warrant further investigation to explore clinical implications.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12977440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketogenic diet can inhibit epileptic seizures by inhibiting RGMa methylation to promote GluA1 palmitoylation in the epileptic rat model.","authors":"Jianing Xu, Liang Huo, Jiatong Liu, Wei Xu, Tao Yu","doi":"10.1186/s12986-026-01090-8","DOIUrl":"10.1186/s12986-026-01090-8","url":null,"abstract":"<p><p>BACKGROUND: This study investigated the relationship between the ketogenic diet, RGMa methylation, and GluA1 palmitoylation in a rat model of epilepsy, aiming to identify a novel mechanism for treating refractory epilepsy with the ketogenic diet. METHODS: Epileptic rats were treated with a ketogenic diet. Hippocampal tissue was analyzed to assess the expression of DNMT1 and DNMT3a proteins, RGMa DNA methylation and protein expression, FAK and zDHHC3 phosphorylation and expression, and GluA1 palmitoylation and expression. The therapeutic effects of the ketogenic diet on seizure frequency were statistically analyzed, along with the correlation between each parameter and treatment outcomes. RESULTS: The ketogenic diet treatment reduced seizure frequency in the epileptic rats. It inhibited RGMa DNA methylation in hippocampal tissue while increasing RGMa expression. Additionally, the diet enhanced GluA1 palmitoylation and reduced its expression on the neuronal membrane. These changes were associated with alterations in FAK/Src and zDHHC3 phosphorylation. CONCLUSION: The ketogenic diet inhibits RGMa DNA methylation, upregulates RGMa expression, and promotes GluA1 palmitoylation, leading to a reduction in seizure frequency and alleviation of refractory epilepsy in the rat model. These effects may be mediated through the RGMa-FAK/Src-zDHHC3 signaling axis. </p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":"30"},"PeriodicalIF":3.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12922386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of plant-based diet with the risk of large-for-gestational-age birth in women with gestational diabetes mellitus.","authors":"Yuhua Yin, Meng Ye, Meiqi Shi, Zelei Miao, Xuhong Wang, Sha Lu, Yingying Wu, Wensheng Hu, Yuanqing Fu","doi":"10.1186/s12986-026-01092-6","DOIUrl":"10.1186/s12986-026-01092-6","url":null,"abstract":"<p><p>BACKGROUND: The distribution of dietary macronutrients is critical for blood glucose management and adverse birth outcomes among pregnant women with gestational diabetes mellitus (GDM); however, the relationship between plant-based food intake and the risk of large-for- gestational-age (LGA) birth is unclear. Here, based on a large-scale birth cohort, we aim to investigate the prospective association between plant-based diet intake and the risk of LGA birth in pregnant women with GDM. METHODS: We included 1768 GDM participants and assessed dietary plant-based diet patterns by constructing plant-based diet index (PDI), healthy plant-based diet index (hPDI) and unhealthy plant-based diet index (uPDI) using data collected from food frequency questionnaires (FFQ). LGA were defined as gender- and gestational age-adjusted birth weight of newborns greater than 90th percentile. RESULTS: We found that individuals in the highest quartile of uPDI had a significantly higher risk of LGA compared to those in the lowest quartile (OR :1.62, 95% CI: 1.02 to 2.62, p = 0.05), after adjusting for potential confounding factors. Moreover, the dose-response analysis indicated a significant nonlinear relationship, with the risk of LGA increasing as uPDI rose from the first to the second quartile (OR: 1.74, 95% CI: 1.06 to 2.88, p = 0.03) and then plateauing upon reaching the third quartile (OR: 2.00, 95% CI: 1.27 to 3.21, p < 0.01). The sensitivity analyses showed that this association was generally robust across different adjustment models, but was attenuated by further adjustment for glycated hemoglobin A1c (HbA1c), which indicated potential mediation roles of HbA1c between unhealthy plant-based diets and LGA risk. CONCLUSIONS: This study suggests that unhealthy plant food intake is a potential risk factor for LGA among pregnant women with GDM. The quality of plant-based foods should be considered when promoting plant-based dietary patterns. </p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12973602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research on dietary sodium with invalid methods does not advance scientific understanding.","authors":"Norm R C Campbell, Francesco P Cappuccio","doi":"10.1186/s12986-025-01057-1","DOIUrl":"10.1186/s12986-025-01057-1","url":null,"abstract":"<p><p>Wuopio et al. (22:104, 2025) examined associations between urinary sodium excretion and metabolic markers using an invalid method (a spot urine sample and the Kawasaki estimating equation (‘spot method’)). The spot method has both high random and systematic error, and has been shown to produce spurious health outcome and disease association. Due to false controversy generated by studies using spot method, it has been recommended not to be used in research associating dietary sodium to health outcomes by major international and national scientific organizations and experts. Wuopio et al. are aware of the methods limitations and concerns about its use but in our opinion did not address these issues in their manuscript. The spot urine method represents a good example of how an inappropriate research method can undermine scientific understanding and generate false controversy.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":"23 1","pages":"17"},"PeriodicalIF":3.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12874762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visceral fat metabolism score and cardiovascular-kidney-metabolic syndrome stages in all-cause and cause-specific mortality: insights from UK Biobank.","authors":"Jilong Bai, Panting Wei, Yao Zhang, Liying Wang, Jinyan Liu, Wenxu Wang, Wan Yu, Difei Wang","doi":"10.1186/s12986-026-01083-7","DOIUrl":"10.1186/s12986-026-01083-7","url":null,"abstract":"<p><p>BACKGROUND: The roles of Cardiovascular-Kidney-Metabolic Syndrome (CKM) staging and the emerging obesity marker Visceral Fat Metabolism Score (METS-VF) in cause-specific mortality, as well as their potential interaction, remain to be further investigated. METHODS: 396,383 UK Biobank participants were analyzed. Primary outcomes included all-cause and cause-specific deaths, including cardiovascular, respiratory, digestive, neurodegenerative diseases, cancer, and other causes. Independent and joint effects of METS-VF and CKM were evaluated using a COX proportional hazards regression model, with multiple sensitivity analyses conducted to verify robustness. Dose–response relationships were visualized using restricted cubic spline (RCS) curves. Receiver operating characteristic (ROC) analyses were conducted to evaluate the discriminative performance of METS-VF for predicting mortality compared with other obesity-related indices. Multiple sensitivity analyses were further performed to assess the robustness of the findings. RESULTS: Over an average follow-up of 12.51 years, 34,471 deaths were recorded. After multivariate adjustment, both METS-VF and CKM stage were associated with all-cause mortality. The hazard ratio for the highest METS-VF quartile was 1.70 (95% CI: 1.61–1.80), and for the highest CKM stage was 2.23 (95% CI: 2.12–2.35). Each 0.1 increase in METS-VF raised the risk of death by 8.2% (CVD), 3.5% (respiratory), 8.8% (digestive), 2.7% (cancer), and 6.9% (other causes). RCS analysis showed a non-linear relationship between METS-VF and mortality. ROC analyses further demonstrated that METS-VF exhibited significantly higher predictive performance for both all-cause and cause-specific mortality compared to other obesity-related indices. Joint analysis revealed that participants with stage IV CKM and high METS-VF had the highest risks of all-cause and cause-specific mortality, with synergistic effects noted for CVD, and digestive mortality. CONCLUSION: High METS-VF and late-stage CKM were associated with increased risks of mortality from multiple causes. For individuals with late-stage CKM, enhanced assessment of METS-VF is recommended to facilitate timely interventions and reduce mortality risk. </p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12964629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}