Metabolism: clinical and experimental最新文献

{"title":"Effect of GLP-1 receptor agonists and co-agonists on atrial fibrillation risk in overweight or obesity: systematic review and meta-analysis of randomized controlled trials","authors":"Paschalis Karakasis ,&nbsp;Konstantinos Vlachos ,&nbsp;Antonios P. Antoniadis ,&nbsp;Konstantinos C. Siontis ,&nbsp;Dimitrios Patoulias ,&nbsp;Nikolaos Fragakis ,&nbsp;Christos S. Mantzoros","doi":"10.1016/j.metabol.2025.156463","DOIUrl":"10.1016/j.metabol.2025.156463","url":null,"abstract":"<div><h3>Background and aims</h3><div>Overweight and obesity represent major modifiable determinants of atrial fibrillation (AF) incidence and arrhythmia outcomes after AF ablation therapy. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and their next-generation co-agonists exert potent weight-lowering and cardiometabolic effects and may therefore confer antiarrhythmic effects. This meta-analysis aimed to quantitatively assess the effect of GLP-1–based therapies on the risk of AF among individuals with overweight or obesity.</div></div><div><h3>Methods</h3><div>A systematic search of Medline, Scopus, and the Cochrane Library was conducted for randomized controlled trials (RCTs) through October 29, 2025. Data were analyzed using random-effects pairwise meta-analysis.</div></div><div><h3>Results</h3><div>Twenty-four RCTs encompassing 40,694 participants were included. Compared with placebo, treatment with GLP-1RAs or co-agonists resulted in a 18 % relative reduction in AF risk (Risk Ratio = 0.82; 95 % confidence interval, 0.70–0.96; <em>P</em> = 0.012; I² = 0 %). No significant between-subgroup differences were observed according to agent type (single-, dual-, or triple-receptor agonists), individual compound, baseline BMI category (overweight/obesity vs. obesity alone), diabetes inclusion criteria, trial design [cardiovascular outcomes trial (CVOT) vs. non-CVOT], or administration route (oral vs. subcutaneous). Meta-regression analyses identified no significant effect modification by the magnitude of weight reduction or concomitant SGLT2 inhibitor use.</div></div><div><h3>Conclusions</h3><div>Among individuals with overweight or obesity, GLP-1RAs and co-agonists were associated with a lower risk of incident AF event. This cardioprotective benefit may, at least in part, operate independently of the magnitude of weight loss.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"175 ","pages":"Article 156463"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1RAs and tirzepatide may reduce heart failure risk in obese but not in non-obese patients with cardiovascular or renal disease: A systematic review and meta-analysis","authors":"Ju Zhang ,&nbsp;Xiangfeng Guan ,&nbsp;Mowei Kong ,&nbsp;Meng Xia ,&nbsp;Yang Yu ,&nbsp;Chunxiang Zhang","doi":"10.1016/j.metabol.2025.156433","DOIUrl":"10.1016/j.metabol.2025.156433","url":null,"abstract":"<div><h3>Background</h3><div>Cardiovascular disease (CVD) and chronic kidney disease (CKD) frequently coexist, with obesity and type 2 diabetes (T2D) being major contributors to adverse outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and tirzepatide have shown cardiorenal benefits beyond glycemic control, but their efficacy across metabolic phenotypes remains unclear.</div></div><div><h3>Methods</h3><div>This review was prospectively registered in PROSPERO (CRD420251088042). PubMed, Embase, Web of Science, and Cochrane Library were searched (January 2015–July 2025) for RCTs comparing GLP-1RAs or tirzepatide with placebo in patients with cardiovascular or renal disease. Subgroup analyses were performed according to T2D and obesity status.</div></div><div><h3>Results</h3><div>A total of 18 RCTs (<em>n</em> = 97,800) involving eight GLP-1RAs and tirzepatide were included, primarily enrolling patients with established cardiovascular or renal disease. GLP-1RAs significantly reduced the risk of the primary composite outcome (RR 0.88, 95 % CI 0.84–0.91, <em>P</em> &lt; 0.001). GLP-1RAs and tirzepatide also significantly reduced the risk of death from any cause (RR 0.88, 95 % CI 0.84–0.92, <em>P</em> &lt; 0.001), and death from cardiovascular causes (RR 0.88, 95 % CI 0.83–0.93, P &lt; 0.001). Although the overall effect of GLP-1RAs on hospitalization for heart failure was not statistically significant (RR 0.92, 95 % CI 0.78–1.08), a potential benefit was observed in obese patients (P for interaction = 0.02), warranting further investigation. GLP-1RAs showed favorable overall safety profile, with a lower incidence of serious adverse events (RR 0.93, 95 % CI 0.89–0.99, <em>P</em> = 0.01) and cardiac adverse events (RR 0.90, 95 % CI 0.85–0.96, <em>P</em> &lt; 0.01) compared with placebo.</div></div><div><h3>Conclusion</h3><div>In patients with cardiovascular or renal disease, GLP-1RAs and tirzepatide provide consistent cardiovascular and renal protection, with a possible benefit in reducing hospitalization for heart failure among individuals with obesity.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"175 ","pages":"Article 156433"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HDL dysfunction: a role in the pathogenesis of cardiometabolic syndrome in chronic HIV infection?","authors":"Konstantinos Markakis ,&nbsp;Leila Fotooh Abadi ,&nbsp;Arnaud Kombe Kombe ,&nbsp;Martinos Christodoulides ,&nbsp;Theodoros Kelesidis","doi":"10.1016/j.metabol.2025.156432","DOIUrl":"10.1016/j.metabol.2025.156432","url":null,"abstract":"<div><div>People living with human immunodeficiency virus (HIV) (PLWH) on antiretroviral treatment (ART) have an increased risk of atherosclerotic cardiovascular disease (CVD) and metabolic syndrome (combinations of adiposity, insulin resistance, hypertension, and dyslipidemia). Together, CVD and metabolic syndrome constitute the cardiometabolic syndrome. Traditional CVD risk factors and high-density lipoproteins (HDL) alterations seem to contribute to the elevated CVD risk. Cumulative evidence suggests that assessing HDL function instead of HDL cholesterol levels (HDL-C) may be a better way to assess cardiometabolic risk. In HIV infection, HIV-1, ART, and the altered function of organs like the liver, gastrointestinal tract, and immune system affect the proteome, lipidome, and metabolism of HDL, ultimately leading to its dysfunction. However, the impact of altered HDL functions on PLWH remains unclear and whether HDL dysfunction reflects and/or contributes to cardiometabolic syndrome in HIV infection (bidirectional cross talk regarding how HDL function impacts the cardiometabolic syndrome and <em>vice versa</em>). Large cohorts of PLWH with variable CVD risk using independent assays of HDL function are needed to elucidate the bidirectional crosstalk between HDL functions and cardiometabolic syndrome. Developing novel treatments to improve HDL function in PLWH may have multiple beneficial results, reducing chronic inflammation and cardiometabolic risk in PLWH. This review aims to summarize the scientific evidence related to the role of HDL functions in HIV and how therapeutic targeting of HDL dysfunction may contribute to reduced cardiometabolic risk in PLWH.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"175 ","pages":"Article 156432"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Addressing the role of 11β-hydroxysteroid dehydrogenase type 1 in the development of polycystic ovary syndrome and the putative therapeutic effects of its selective inhibition in a preclinical model” [Metab Clin Exp 119 (2021) 154749 1–14 [METABOLISM-D-20-01502R3]]","authors":"Xinyu Li ,&nbsp;Shuanggang Hu ,&nbsp;Qinling Zhu ,&nbsp;Guangxin Yao ,&nbsp;Jufang Yao ,&nbsp;Jiaxing Li ,&nbsp;Yuan Wang ,&nbsp;Ying Ding ,&nbsp;Jia Qi ,&nbsp;Rui Xu ,&nbsp;Hanting Zhao ,&nbsp;Zhenyi Zhu ,&nbsp;Yanzhi Du ,&nbsp;Kang Sun ,&nbsp;Yun Sun","doi":"10.1016/j.metabol.2025.156437","DOIUrl":"10.1016/j.metabol.2025.156437","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"175 ","pages":"Article 156437"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FAM83A acts as an amplifier for lipogenic signaling to facilitate the pathogenesis of metabolic dysfunction-associated steatohepatitis","authors":"Yang Zhou ,&nbsp;Yuhang Dai ,&nbsp;Mengyao Qin ,&nbsp;Yecheng Li ,&nbsp;Lunan Shi ,&nbsp;Hao Chen ,&nbsp;Hui Fan ,&nbsp;Yunli Yu ,&nbsp;Le Guo ,&nbsp;Jing Xiong","doi":"10.1016/j.metabol.2025.156462","DOIUrl":"10.1016/j.metabol.2025.156462","url":null,"abstract":"<div><h3>Background &amp; aims</h3><div>Metabolic dysfunction-associated fatty liver disease (MAFLD) and its more severe manifestation, metabolic-associated steatohepatitis (MASH), are intimately linked to disturbances in lipid metabolism. Although downstream signaling pathways of epidermal growth factor receptor (EGFR), including extracellular signal-regulated kinase (ERK) and proto-oncogene serine/threonine kinase (RAF1), exhibited heightened activation during MASH progression, their specific roles and underlying mechanisms in driving MASH pathogenesis remain inadequately elucidated.</div></div><div><h3>Methods</h3><div>A comprehensive transcriptomic analysis was performed to indentify key genes involved in MAFLD development. Murine models with hepatocyte-specific depletion or overexpression of FAM83A were subjected to either a high-fat diet (HFD) for 8 or 14 weeks to simulate simple steatosis (MAFL) and MASH, respectively, or a choline-deficient high-fat diet (CDAHFD) to accelerate MASH progression.</div></div><div><h3>Results</h3><div>FAM83A, recognized as a downstream effector of EGFR that activates the ERK signaling pathway, was predominantly expressed in hepatoctyes and upregulated during MASH pathogenesis in both animal models and clinical patients. Hepatocyte-specific FAM83A knockout delayed MASH progression and mitigated hepatic inflammation and fibrosis. Conversely, overexpression of FAM83A exacerbated MASH pathology, evidence by increased lipid accumulation, inflammation and fibrosis. Mechanistically, insulin induces transcriptional expression of FAM83A, which physically bound to RAF1, enhancing its phosphorylation and subsequent ERK signaling activation. Furthermore, FAM83A-mediated upregulatation of lipogenic gene expression and lipogenesis was significantly inhibited by the treatment of RAF1 inhibitor sorafenib or ERK inhibitor PD98059.</div></div><div><h3>Conclusions</h3><div>FAM83A promotes MASH pathogenesis by interacting with RAF1 to activate ERK signaling, thereby stimulating fatty acid and cholesterol biosynthesis. Targeting this axis may offer therapeutic potential for MASH and metabolic dyslipidemia.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"175 ","pages":"Article 156462"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting lipid metabolism in neurodegenerative diseases: From experimental to clinical","authors":"Junpeng Long ,&nbsp;Shasha Liu ,&nbsp;Yaning Shi ,&nbsp;Chanjuan Zhang ,&nbsp;Li Qin ,&nbsp;Qidi Ai","doi":"10.1016/j.metabol.2025.156436","DOIUrl":"10.1016/j.metabol.2025.156436","url":null,"abstract":"<div><div>The human brain, despite accounting for only 2 % of total body weight, exhibits an exceptionally high lipid content (approximately 20 % of its mass), highlighting the critical role of lipid metabolism in maintaining neural homeostasis and function. Neurodegenerative diseases—including Alzheimer's disease (AD), Parkinson's disease (PD), stroke, Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS)—are characterized by progressive neuronal dysfunction and myelin degeneration. These conditions predominantly affect aging populations and represent a growing global health challenge. While aging remains the primary risk factor, compelling evidence now underscores the involvement of dysregulated lipid metabolism in their pathogenesis. However, the precise mechanisms linking dynamic lipid metabolic alterations to disease progression remain incompletely elucidated. This review systematically examines the multifaceted contributions of lipid metabolism to neurodegenerative processes and critically assesses emerging therapeutic strategies that target lipid pathways for the treatment of neurodegenerative disorders.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"175 ","pages":"Article 156436"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging roles of arginine metabolism in skeletal health and disease","authors":"Sibo Wang ,&nbsp;Qian Ren ,&nbsp;Yansheng Huang ,&nbsp;Yibo Ma ,&nbsp;Xuefang Zhang ,&nbsp;Yuan Liu ,&nbsp;Baorong He ,&nbsp;Liang Yan","doi":"10.1016/j.metabol.2025.156451","DOIUrl":"10.1016/j.metabol.2025.156451","url":null,"abstract":"<div><div>Arginine, as a semi-essential amino acid, plays a pivotal role in bone metabolism and orthopedic diseases. Beyond its function in protein synthesis, arginine serves as a crucial precursor for Nitric Oxide (NO), polyamines, and proline, profoundly influencing osteoblast differentiation, osteoclast activation, immune responses, and angiogenesis. Research indicates that abnormalities in arginine metabolism—such as imbalances in NO synthase activity, upregulation of arginase, or abnormal expression of protein arginine methyltransferases—are closely associated with the onset and progression of osteoporosis, rheumatoid arthritis, osteoarthritis, and bone tumors. Simultaneously, the arginine pathway intertwines with oxidative stress, inflammatory responses, and epigenetic regulation, forming a complex “metabolism-immunity-bone” network. In materials science, arginine has been integrated into various biomaterial systems, including Poly (lactic-<em>co</em>-glycolic acid) (PLGA) scaffolds, chitosan hydrogels, hydroxyapatite composites, and RGD-functionalized polymers, significantly enhancing osteogenic, angiogenic, and immunomodulatory capabilities. Despite ongoing research advancements, challenges persist in understanding the environment-dependent effects of arginine, optimizing dosage, and achieving clinical translation. This review systematically summarizes the mechanistic roles of arginine in bone metabolism regulation and its application progress in engineered materials, offering novel therapeutic insights and research directions for preventing and treating diseases such as osteoporosis, arthritis, and bone tumors.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"175 ","pages":"Article 156451"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145570288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic reprogramming in diabetic foot ulcers: mechanisms, therapeutic implications and future perspectives","authors":"Li Jinyi ,&nbsp;Ding Xianguang ,&nbsp;Ding Yuhan ,&nbsp;Huang Haoyue ,&nbsp;Xia Zhongyu ,&nbsp;Wang Lianhui ,&nbsp;Jianda Xu","doi":"10.1016/j.metabol.2025.156455","DOIUrl":"10.1016/j.metabol.2025.156455","url":null,"abstract":"<div><div>As a devastating complication, diabetic foot ulcer (DFU) is characterized by chronic, nonhealing wounds due to vasculopathy and neuropathy. It has emerged as a most challenging chronic disease worldwide, affecting millions of people worldwide. The higher mortality and disability rates urgently require innovative therapeutic strategies. Recently, different from nanotechnology, metabolic reprogramming is believed to be associated with the occurrence and progression of various diseases (including cancer, obesity and neurodegenerative diseases). They can alter their cellular metabolism (involving glucose, lipid, and amino acid metabolism) to cope with different external stimuli and pressures. As a novel potential strategy, metabolic reprogramming also exhibits great potential to improve the wound healing of DFU. This review aims to summarize the current knowledge, biological characteristics, and underlying mechanisms of metabolic reprogramming in DFU. And we propose their potential therapeutic implications to improve wound healing and prevent complications in DFU. In addition, we also highlight the current challenges and the future perspectives.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"175 ","pages":"Article 156455"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of Yin Yang 1 (YY1) overexpression in mature adipocytes promotes dysfunctional adipose tissue and systemic insulin resistance in mice","authors":"Line Pedersen ,&nbsp;Christy M. Gliniak ,&nbsp;Thomas Myhre Dale ,&nbsp;Qingzhang Zhu ,&nbsp;Chao Li ,&nbsp;Jan-Bernd Funcke ,&nbsp;Clair Crewe ,&nbsp;Jiahui Luo ,&nbsp;Lauren Palluth ,&nbsp;Yi Zhu ,&nbsp;Philipp E. Scherer","doi":"10.1016/j.metabol.2025.156439","DOIUrl":"10.1016/j.metabol.2025.156439","url":null,"abstract":"<div><div>The ubiquitous transcription factor Ying Yang 1 (YY1) plays a fundamental role in multiple biological processes and is believed to regulate up to 10 % of all human genes. In thermogenic brown adipose tissue, YY1 has been linked to controlling mitochondrial gene expression and regulating cellular oxidative respiration, protecting against diet-induced obesity and alterations in energy balance. The role of YY1 in non-thermogenic, white adipose tissue, on the other hand, remains largely unknown. Here, we show that adipocyte-specific induction of YY1 promotes dysfunctional adipose tissue and systemic insulin resistance in mice. Long-term YY1 induction in mature adipocytes leads to reduced weight gain, systemic insulin resistance, and increased liver steatosis in comparison to control littermates. In contrast, brown adipose tissue-specific YY1 overexpression has little effect on mice fed a high-fat diet. In an obesogenic environment, acute ectopic adiponectin promoter-driven YY1 expression promotes weight loss, cell death, and adipose tissue inflammation. Underlying the observed reduction in adipose tissue mass, we find that YY1 controls gene networks related to adipose tissue expansion, lipid anabolic pathways (hypertrophy), and hyperplasia (adipogenesis). Taken together, our results demonstrate novel roles of <em>Yy1</em> in white adipose tissue. This versatile transcription factor regulates central aspects of white adipose tissue biology that are essential for maintaining whole-body physiology.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"175 ","pages":"Article 156439"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the obesity paradox in cancer: An umbrella review of protective associations and evidence credibility across 13 malignancies","authors":"Lulin Yu ,&nbsp;Jing Yuan ,&nbsp;Mingxian Meng ,&nbsp;Hejing Pan ,&nbsp;Long Ge ,&nbsp;Liaoyao Wang ,&nbsp;Xuanlin Li","doi":"10.1016/j.metabol.2025.156461","DOIUrl":"10.1016/j.metabol.2025.156461","url":null,"abstract":"<div><h3>Background</h3><div>The “obesity paradox” in cancer remains controversial amid inconsistent meta-analyses. This umbrella review re-analyses evidence across 13 malignancies using pre-specified credibility criteria to clarify associations.</div></div><div><h3>Methods</h3><div>We conducted an umbrella review of systematic reviews and meta-analyses investigating obesity and cancer incidence or prognosis. PubMed, Embase, and Cochrane Library were searched from inception to August 2025. Evidence credibility was graded using the following criteria: statistical significance, heterogeneity, 95 % prediction intervals, small-study effects, excess significance bias, and methodological quality assessment.</div></div><div><h3>Findings</h3><div>Based on 33 included articles (comprising 145 associations across 13 cancer types), only two associations met the convincing evidence criteria: higher BMI was associated with a reduced incidence of oral cancer (relative risk [RR] = 0.93, 95 % CI: 0.91–0.96), and excess weight was associated with a reduced incidence of lung cancer in the Chinese population (odds ratio [OR] = 0.68, 95 % CI: 0.59–0.79). Highly suggestive evidence has revealed associations in lung cancer (reduced incidence, fewer surgical complications and prolonged cancer-specific survival), breast cancer (reduced incidence and decreased likelihood of lymph node metastasis), renal cell carcinoma (prolonged overall survival) and prostate cancer (prolonged overall survival). Of the remaining associations, 20 were suggestive, 51 weak, and 53 non-significant.</div></div><div><h3>Conclusions</h3><div>Only 21 (14 %) meta-analyses provided convincing or highly suggestive evidence, demonstrating potential associations of obesity in specific oncological contexts pertaining to both reduced incidence risk and improved prognostic outcomes. This synthesis also highlights critical gaps in current evidence, emphasising the need for standardised adiposity metrics, more prudent stratification, and rigorous methodology.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"175 ","pages":"Article 156461"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}