Metabolism open最新文献

{"title":"Vitamin D supplementation at low (600 IU/day) or higher dose (3,750 IU/day) does not improve insulin resistance markers at one year: A randomized controlled trial","authors":"Nancy Safwan ,&nbsp;Christos S. Mantzoros ,&nbsp;Maya Rahme ,&nbsp;Rafic Baddoura ,&nbsp;Georges Halaby ,&nbsp;Ghada El-Hajj Fuleihan","doi":"10.1016/j.metop.2025.100357","DOIUrl":"10.1016/j.metop.2025.100357","url":null,"abstract":"<div><h3>Aims</h3><div>To compare the performance of newer insulin resistance (IR) indices, triglyceride glucose index (TyG) and metabolic score for IR (METS-IR), with previous markers HOMA-IR and McAuley-IR, and assess the impact of one-year of vitamin D supplementation, at two doses, on these indices in overweight, elderly individuals.</div></div><div><h3>Methods</h3><div>Exploratory analyses from a double-blind, multicenter randomized controlled trial involved overweight elderly participants with baseline serum 25-hydroxyvitamin D [25(OH)D] levels of 10–30 ng/ml (clinicaltrial.gov: NCT01315366). Participants received 1000 mg calcium citrate/day and vitamin D supplementation at a low-dose of 600 IU/day, or high-dose of 3750 IU/day.</div></div><div><h3>Results</h3><div>221 participants received low or high-dose vitamin D supplementation. Mean age was 71 ± 5 years, BMI 30 ± 4 kg/m², 25(OH)D 20 ± 7 ng/ml, with 55 % female and 69 % with prediabetes. There were no significant baseline differences except for HDL levels (p = 0.04). TyG was notably increased in the high-dose group (p = 0.02). Mixed linear model analysis showed a greater increase in serum 25(OH)D in the high-dose group compared to the low-dose, with decreases in PTH, cholesterol, and LDL independent of dose. TyG and METS-IR did not differ by dose, time, or dose∗time interaction. Subgroup analyses by sex, baseline 25(OH)D cut-off, and glucose tolerance status were null. <em>Fok</em>I polymorphism showed a significantly greater METS-IR in the high-dose arm, disappeared after adjusting for fat mass. McAuley-IR was the best IR index compared to TyG and METS-IR, both at baseline and 12 months.</div></div><div><h3>Conclusions</h3><div>Vitamin D supplementation at 3750 IU/d over one-year did not improve IR markers, including TyG and METS-IR.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100357"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Truncated variant rs373056577 confers increased risk of type 2 diabetes and missense variant rs121912717 is associated with hypertriglyceridemia in Bangladeshi population","authors":"Shomoita Sayed ,&nbsp;Abdullah Al Saba ,&nbsp;Imrul Hasan ,&nbsp;Rafia Rahat ,&nbsp;Mohammad Sayem ,&nbsp;Akio Ebihara ,&nbsp;A.H.M. Nurun Nabi","doi":"10.1016/j.metop.2025.100364","DOIUrl":"10.1016/j.metop.2025.100364","url":null,"abstract":"<div><div>This study investigates the association of allelic and genotypic variations of rs121912717 and rs373056577 within APOA1 and APOA2 genes, respectively with the risk of type 2 diabetes (T2D). In this cross-sectional study, real-time quantitative PCR with specific Taqman probes was used to determine the genotypic and allelic frequencies of rs121912717 and rs373056577 in 300 unrelated Bangladeshi individuals (Healthy = 144, T2D patients = 156). Logistic regression analysis was performed to investigate the association of genotypic and allelic frequencies of these SNPs with respect to T2D under different inheritance models. Neither allelic nor genotypic frequencies of rs121912717 within APOA1 showed any significant association with T2D. Genotypes with respect to rs373056577 within APOA2 showed significant association with the risk of T2D under co-dominant heterozygous model (GG vs GA) [OR (95 %CI): 2.64 (1.32–5.59), p = 0.008], dominant [OR (95 %CI): 2.31 (1.24–4.49), p = 0.01] and over-dominant [OR (95 %CI): 2.62 (1.31–5.53), p = 0.008] models without adjusting for age, gender and BMI. After adjusting for age, gender and BMI, the A allele of rs373056577 showed significant association with T2D only in the dominant model [OR (95 %CI): 3.20 (1.12–10.51), p = 0.04]. Also, A allele of rs373056577 demonstrated significant association with the risk of T2D compared to allele G with [OR (95 %CI): 2.90 (1.15–8.14), p = 0.03] and without adjusting for confounders [OR (95 %CI): 1.97 (1.14–3.52), p = 0.02]. The genotypic frequency was significantly associated with T2D in codominant, dominant, and overdominant models in male participants when a gender-stratified analysis was conducted for rs373056577. However, when the logistic regression analysis was adjusted for age and BMI, the association was not significant in any of the models with respect to rs373056577 for male participants. On the other hand, gender-stratified regression analyses revealed no significant association with T2D before and after adjusting for age and BMI with respect to both allelic and genotypic frequencies of rs121912717. Individuals with CT genotype of rs121912717 had significantly higher triglyceride levels (322.2 mg/dL) compared to those harboring CC genotype (202.8 mg/dL) with or without adjusting for age, gender, BMI and disease status of the study participants. In conclusion, this study revealed that individuals harboring the allele A of rs373056577 possessed an increased risk of developing T2D and individuals having CT genotype of rs121912717 had increased triglyceride levels. The result of this study needs to be validated in a larger cohort for a more robust assessment.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100364"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic regulation of Th17 and Treg cell balance by the mTOR signaling","authors":"Zhengzheng Wang ,&nbsp;Zhen Xu ,&nbsp;Ming Zong ,&nbsp;Lieying Fan","doi":"10.1016/j.metop.2025.100369","DOIUrl":"10.1016/j.metop.2025.100369","url":null,"abstract":"<div><div>The balance between T helper type 17 (Th17) and regulatory T (Treg) cells is crucial for maintaining immune homeostasis. The breakdown of this equilibrium is strongly associated with autoimmune disorders, though the regulatory mechanism of the Th17/Treg plasticity is less well demonstrated. The glycolytic metabolism plays a vital role in regulating the Th17/Treg cell differentiation. The review addressed the importance of mammalian target of rapamycin (mTOR) signaling in the glycolysis pathway attributed to Th17/Treg cell balance and consequence. Notably, we discuss the consequences of its equilibrium that lead to various autoimmune diseases, which might provide a new insight into the potentially therapeutic drug target for autoimmune disorders.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100369"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PCSK9-promoted LDLR degradation: Recruitment or prevention of essential cofactors?","authors":"Rong Li ,&nbsp;Cindy Xinyi Zhang ,&nbsp;Junli Liu ,&nbsp;Da-wei Zhang","doi":"10.1016/j.metop.2025.100362","DOIUrl":"10.1016/j.metop.2025.100362","url":null,"abstract":"","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100362"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144272116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A direct effect of sulfatide against development of fibrosis","authors":"Rikke Thea ,&nbsp;Karsten Buschard","doi":"10.1016/j.metop.2025.100368","DOIUrl":"10.1016/j.metop.2025.100368","url":null,"abstract":"","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100368"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive profiling of candidate biomarkers and immune infiltration landscape in metabolic dysfunction-associated steatohepatitis","authors":"Zhangliu Jin ,&nbsp;Jianyun Cao ,&nbsp;Zhaoxun Liu ,&nbsp;Mei Gao ,&nbsp;Hailan Liu","doi":"10.1016/j.metop.2025.100366","DOIUrl":"10.1016/j.metop.2025.100366","url":null,"abstract":"<div><h3>Background</h3><div>The incidence of metabolic dysfunction-associated steatohepatitis (MASH) is increasing, with an incompletely understood pathophysiology involving multiple factors, particularly innate and adaptive immune responses. Given the limited pharmacological treatments available, identification of novel immune metabolic targets is urgently needed. In this study, we aimed to identify hub immune-related genes and potential biomarkers with diagnostic and predictive value for MASH patients.</div></div><div><h3>Methods</h3><div>The GSE164760 dataset from the Gene Expression Omnibus was utilized for analysis, and the R package was used to identify differentially expressed genes. Immune-related differentially expressed genes (IR-DEGs) were identified by comparing the overlap of differentially expressed genes with well-known immune-related genes. Furthermore, the biological processes and molecular functions of the IR-DEGs were analyzed. To characterize the hub IR-DEGs, we employed a protein-protein interaction network. The diagnostic and predictive values of these hub IR-DEGs in MASH were confirmed using GSE48452 and GSE63067 datasets. Finally, the significance of the hub IR-DEGs was validated using a mouse model of MASH.</div></div><div><h3>Results</h3><div>A total of 91 IR-DEGs were identified, with 61 upregulated and 30 downregulated genes. Based on the protein-protein interaction network, FN1, RHOA, FOS, PDGFRα, CCND1, PIK3R1, CSF1, and FGF3 were identified as the hub IR-DEGs. Moreover, we found that these hub genes are closely correlated with immune cells. Notably, the validation across two independent cohorts as well as a murine MASH model confirmed their high diagnostic potential.</div></div><div><h3>Conclusion</h3><div>The hub IR-DEGs, such as FN1, RHOA, FOS, PDGFRα, CCND1, PIK3R1, CSF1, and FGF3, may enhance the diagnosis and prognosis of MASH by modulating immune homeostasis.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100366"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential role of adipokines and hepatokines in age-related ocular diseases","authors":"Stavroula Almpanidou,&nbsp;Ilias D. Vachliotis,&nbsp;Antonis Goulas,&nbsp;Stergios A. Polyzos","doi":"10.1016/j.metop.2025.100365","DOIUrl":"10.1016/j.metop.2025.100365","url":null,"abstract":"<div><div>Age-related ocular diseases, including diabetic retinopathy (DR), age-related macular degeneration (AMD), cataract and glaucoma may lead to visual impairment and even to blindness. Metabolic diseases, such as obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) have emerged as potential risk factors of age-related ocular diseases, especially DR. Visceral adiposity has been associated with increased risk of DR and AMD in most clinical studies, although body mass index has to-date provided conflicting association with DR and AMD. In addition, obesity is recognized as a risk factor of cataract and glaucoma. Similarly to obesity, MASLD appears to be associated with DR in patients with type 1 diabetes mellitus, but probably not in those with type 2 diabetes mellitus. A potential positive association between MASLD and AMD, glaucoma and cataract is supported by limited evidence to-date, thus needing further investigation. Altered secretion patterns of adipokines (adiponectin, leptin, lipocalin-2, resistin) and hepatokines [adropin, fetuin-A, fibroblast growth factor (FGF)-21, retinol binding protein (RBP)-4] seem to disrupt ocular homeostasis and contribute to the development of age-related ocular diseases in the context of obesity and MASLD. In this regard, novel adipokine-based and hepatokine-based therapies may be added to the treatment options for ocular diseases in the future. This narrative review aimed to summarize evidence on the interconnection of obesity and MASLD with age-related ocular diseases, with a specific focus on the roles of adipokines and hepatokines as mediators of these potential associations.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100365"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143854373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Higher serum uric acid levels and risk of all-cause mortality in general population: a systematic review and meta-analysis","authors":"Md Golam Rabbani ,&nbsp;Sheikh M. Alif ,&nbsp;Cammie Tran ,&nbsp;Amanda J. Rickard ,&nbsp;Lisa Demos ,&nbsp;John J. McNeil ,&nbsp;Md Nazmul Karim","doi":"10.1016/j.metop.2025.100371","DOIUrl":"10.1016/j.metop.2025.100371","url":null,"abstract":"<div><h3>Background</h3><div>Population-based studies have reported a relationship between high serum uric acid (SUA) levels and all-cause mortality; however, findings are inconsistent. To address this issue, we conducted a meta-analysis of general population-based studies.</div></div><div><h3>Methods</h3><div>A systematic search was conducted in PubMed, Ovid Medline, EMBASE, and Web of science to identify relevant peer-reviewed articles using pre-specified search terms. Population-based cohort studies investigating the association between SUA levels and all-cause mortality were included. Risk ratios (RR) for all-cause mortality were calculated for higher and lower SUA levels based on data reporting on exposure and outcome. A meta-analysis based on a log-transformed random effect maximum likelihood model was used to obtain summary risk estimates. Heterogeneity was assessed through subgroup analysis and meta-regression of the study-level covariates.</div></div><div><h3>Results</h3><div>Thirty-four studies with more than 2.5 million participants were identified and analysed. Higher SUA levels were associated with an increased risk of all-cause mortality (RR: 1.32; 95 % confidence intervals (CIs):1.26–1.39, p &lt; 0.001). The risk of mortality was higher in women (RR:1.91; 95 %CI:1.40–2.61, p &lt; 0.001) compared to men (RR:1.16; 95 %CI:1.08 1.24, p &lt; 0.001). Subgroup analyses suggested that middle-aged adults (RR: 1.52, 95 %CI: 1.35–1.68), individuals living in OECD countries (RR:1.39, 95 %CI:1.28–1.49) and those of Caucasian ethnicity (RR:1.43, 95 %CI:1.35–1.51) reported a greater impact of elevated SUA levels on all-cause mortality.</div></div><div><h3>Conclusions</h3><div>Higher SUA levels were associated with a significant increase in the risk of all-cause mortality, with women appearing to be at greater risk than men. These findings highlight the need for research into mechanisms underlying the association between SUA and mortality and the reason for the sex difference identified.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100371"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of DNA glycation in the prediabetic State: Early indicator of glycemic stress","authors":"Tanish Baweja ,&nbsp;Abhishek Dikshit ,&nbsp;Shazia Bano ,&nbsp;Sanjiv Kumar Bansal ,&nbsp;Sana Alam","doi":"10.1016/j.metop.2025.100372","DOIUrl":"10.1016/j.metop.2025.100372","url":null,"abstract":"<div><h3>Introduction</h3><div>Glycation of nucleic acids secondary to hyperglycemia can lead to structural alterations and the formation of neoantigens. These molecular changes may elicit an early immune response. This study investigates the interaction between serum autoantibodies from prediabetic individuals and fructose-glycated human placental DNA, aiming to assess DNA glycation as a potential early indicator of glycemic stress.</div></div><div><h3>Design</h3><div>and Methods: To investigate structural modifications in DNA produced by glycation, purified placental DNA was incubated with fructose (25 mM) at 37 °C for 5, 10, and 15 days, followed by spectrophotometric analysis. Peripheral blood samples were collected from 50 normoglycemic (mean age: 39.70 ± 6.63 years; 26 males, 24 females) and 50 prediabetic (mean age: 40.84 ± 5.44 years; 23 males, 27 females) adult patients, matched for age, sex, body mass index, and socio-economic conditions. The presence of circulating antibodies against glycated DNA was evaluated using direct and competitive ELISA.</div></div><div><h3>Results</h3><div>Fructose-mediated glycation of DNA resulted in hyperchromicity and a new absorbance peak at 360 nm, indicating structural modification. Direct ELISA revealed significantly higher levels of anti-DNA autoantibodies in prediabetic sera (0.367 ± 0.225) compared to controls (0.239 ± 0.118; p = 0.003). Competitive ELISA showed that these antibodies had greater specificity for glycated DNA, with maximum inhibition by fructose-modified DNA at 37.86 ± 2.57 %, versus 23.01 ± 2.33 % for native DNA (p &lt; 0.01).</div></div><div><h3>Conclusion</h3><div>The study concludes that DNA glycation occurs in prediabetic patients with intermediate hyperglycemia as a result of high blood glucose. This suggests that glycated DNA may serve as an early molecular indicator of glycemic stress, with potential applications in risk assessment and early detection strategies for individuals at risk of progressing to type 2 diabetes.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100372"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144229659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of blood manganese levels with non-alcoholic fatty liver disease in NHANES 2017–2020: A retrospective cross-sectional study","authors":"Qian Xue ,&nbsp;Hongju Chen","doi":"10.1016/j.metop.2025.100358","DOIUrl":"10.1016/j.metop.2025.100358","url":null,"abstract":"<div><h3>Objective</h3><div>This study investigates the link between blood manganese (Mn) levels and non-alcoholic fatty liver disease (NAFLD) in a U.S. adult population.</div></div><div><h3>Background</h3><div>The role of manganese in NAFLD remains poorly understood. However, the NHANES database offers valuable data on blood manganese levels and metabolic status for 6278 subjects in the United States, facilitating the study of this relationship.</div></div><div><h3>Methods</h3><div>To investigate the relationship between blood manganese (Mn) levels and NAFLD, we conducted a <em>t</em>-test to compare Mn levels between participants with and without NAFLD. Participants were categorized into quartiles based on their blood Mn levels. We then employed multiple logistic regression analysis and sensitivity analyses to further examine the Mn-NAFLD relationship.</div></div><div><h3>Results</h3><div>The NAFLD group had a significantly higher blood manganese level (10.0 ± 3.7 μg/L, P &lt; 0.05) than the control group. Stratifying 6278 subjects by blood manganese quartiles showed increased NAFLD odds in higher quartiles (Q2-Q4) vs. Q1 (ORs: 1.49, 1.37, 1.49). The Mn-NAFLD relationship followed an inverted L-shaped curve, peaking at 8.52 μg/L.</div></div><div><h3>Conclusions</h3><div>Elevated levels of manganese in the blood have been shown to be associated with an increase in the risk of NAFLD, and blood manganese values can be utilized as a marker for assessing NAFLD.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100358"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}