Nutrition & Metabolism最新文献

{"title":"Retraction Note: An interpretable machine learning model for precise prediction of biomarkers for intermittent fasting pattern.","authors":"Xiaoli Hu, Qingjun Xu, Xuan Ma, Lin Li, Yongning Wu, Feifei Sun","doi":"10.1186/s12986-026-01218-w","DOIUrl":"10.1186/s12986-026-01218-w","url":null,"abstract":"","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":"23 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112808","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":"Trimethylamine N-oxide and major adverse cardiac and cerebrovascular events: results of umbrella review and meta-analysis.","authors":"Rima Obeid, Lorenz Mohr, Bryan A White, Gunnar H Heine, Insa Emrich, Juergen Geisel, R Colin Carter","doi":"10.1186/s12986-026-01214-0","DOIUrl":"10.1186/s12986-026-01214-0","url":null,"abstract":"<p><strong>Background: </strong>Circulating trimethylamine N-oxide (TMAO) may be a causal factor or marker for major adverse cardiac and cerebrovascular events (MACE), but evidence in humans is limited to observational studies with inherent uncertainties.</p><p><strong>Methods: </strong>We conducted an umbrella systematic review and meta-analysis of human studies. The search in MEDLINE, Web of Science, Cochrane Library and PROSPERO (last updated in February 2025) identified 120 publications that met our inclusion criteria.</p><p><strong>Results: </strong>The pooled hazard ratio (HR) and 95% confidence intervals (95%CIs) from 34 cohort studies on TMAO and MACE = 1.20 (1.12-1.27), the prediction interval (PI) was 0.93-1.54, and I² = 73.3%. After correction for publication bias (p < 0.001 Egger's test), the pooled HR (95%CIs) was 1.10 (1.03-1.17). The pooled odds ratio (95%CIs) from 18 case-control studies after accounting for publication bias was 1.05 (0.94-1.18). As a diagnostic test, the estimated pooled area under the curve (95%CIs) for TMAO was 72.8 (68.8-77.1)%, PI = 54.7%-97.1%, I² = 93.8%, n = 24 studies. The mean (95%CIs) sensitivity and specificity of TMAO were 65.3 (56.1-74.5)% and 79.0 (65.4-92.6)%, respectively. The data did not suggest a threshold for elevated TMAO concentrations.</p><p><strong>Conclusions: </strong>Previously reported association estimates between TMAO and MACE in human studies are systematically overestimated. The results do not support TMAO being a causal factor or marker of MACE and related conditions. Harmonisation of TMAO measurements between labs and cohort studies in healthy people that address confounding factors remain critically needed.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":"23 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031048","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":"Correction: The role of dietary factors in the prevention and management of inflammatory bowel disease: a comprehensive review.","authors":"Elyas Nattagh-Eshtivani, Hanieh Barghchi, Amir Hossein Mansouri, Pegah Rahbarinejad, Amin Mokari-Yamchi, Mehdi Barati, Mohammad Rashidmyvan, Ali Jafazadeh Esfehani, Alireza Mohammadzadeh, Zachry Clyton, Parisa Marabi, Saeedeh Talebi, Naseh Pahlavani","doi":"10.1186/s12986-026-01191-4","DOIUrl":"10.1186/s12986-026-01191-4","url":null,"abstract":"","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":"23 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819228","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":"Physical activity and metabolic syndrome in relation to incident dementia in UK biobank.","authors":"Yiqun Li, Xiao Ren, Minglan Jiang, Pinni Yang, Yiming Jia, Lulu Sun, Ruirui Wang, Mengyao Shi, Xiaowei Zheng, Zhengbao Zhu, Yonghong Zhang","doi":"10.1186/s12986-025-01058-0","DOIUrl":"https://doi.org/10.1186/s12986-025-01058-0","url":null,"abstract":"<p><strong>Background: </strong>The purpose of this study was to investigate the relationship among physical activity (PA), metabolic syndrome (MetS) and dementia based on UK Biobank.</p><p><strong>Methods: </strong>A total of 220,372 dementia-free participants over the age of 50 had available data for outcomes and exposures components were included. Four PA groups [High, Medium, Low and No Moderate-to-vigorous PA (MVPA)], two MetS groups (MetS and No MetS) and eight joint groups were categorized to explore the effects of PA level and MetS status on dementia outcomes. Multivariate Cox proportional hazards regression model was used to explore the associations between PA, MetS and new-onset dementia.</p><p><strong>Results: </strong>During a median follow-up of 13 years, 4778 all-cause dementia [ACD, including 2997 Alzheimer's disease (AD) and 960 vascular dementia (VD) events] were recorded. In multivariate models adjusting for genetic and biological factors, lifestyle factors and socioeconomic factors, participants with MetS had a 25% increase in the risk of dementia. In terms of PA, the incidence of dementia in individuals without MVPA increased by 46%. Cox proportional hazards regression and Kaplan-Meier analysis all showed that participants with MetS and No MVPA had remarkable highest risk in eight joint groups (for ACD, 1.43 (1.01-2.02); for AD, 1.61 (0.73-1.84); for VD, 3.14 (1.60-6.14), compared with the reference group of No MetS-High PA).</p><p><strong>Conclusions: </strong>There is a synergistic correlation of MetS and PA level with dementia (ACD, AD and VD), which is significantly exacerbated in participants with MetS and No MVPA. Even low levels of PA may also effectively decrease the harmful associations between MetS and dementia.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":"23 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224691","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":"B-vitamin-associated miRNAs are enriched in pathways related to cell proliferation - insights from the general population.","authors":"Sandra Van der Auwera, Sabine Ameling, Nele Friedrich, Matthias Nauck, Uwe Völker, Henry Völzke, Hans J Grabe","doi":"10.1186/s12986-026-01177-2","DOIUrl":"10.1186/s12986-026-01177-2","url":null,"abstract":"<p><strong>Background: </strong>Vitamins are essential micronutrients that play crucial roles in human health, including immune function, cell development, energy metabolism, and the function of the nervous system. Within the body, vitamins can activate and modulate various biological pathways by acting as cofactors for enzymes. The objective of this study was to identify microRNAs (miRNAs) associated with the serum concentration of specific vitamins in the general population, and subsequently identifying vitamin associated biological systems and diseases potentially influenced by post-transcriptional regulation of these miRNAs.</p><p><strong>Methods: </strong>Data from the population-based Study of Health in Pomerania (SHIP-TREND-0, N = 792) were utilized to examine the associations between vitamin B12 and folic acid (vitamin B9) and 181 miRNAs. Multivariate linear models were employed, adjusting for potential confounders such as age, sex, platelet count, BMI, hemolysis, batch effects, and seasonality. Publicly available databases were used to identify biological pathways influenced by those significant miRNAs.</p><p><strong>Results: </strong>After correction for multiple comparisons, eight miRNAs were found to be positively associated with folic acid, and six miRNAs were positively associated with vitamin B12. The miRNAs significantly associated with folic acid were predominantly found in red blood cells, while those associated with vitamin B12 were associated with red blood cells and T-cells according to the miR-Blood database. Analyses of over-represented miRNAs revealed enrichment in processes related to cell-cycle regulation, DNA synthesis, metabolic processes, and erythropoiesis. In accordance to the known positive role of folic acid and vitamin B12 in pregnancy, nearly all significant miRNAs have been identified to be associated with pregnancy outcomes based on previous research.</p><p><strong>Conclusions: </strong>The analyses revealed that several miRNAs are related to vitamin levels and that these miRNAs are associated with processes such as cell proliferation and human fertility. These miRNAs could be interesting targets for further clinical applications.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":"23 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13390333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562631","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":"Work-to-sleep ratio as a novel marker of NAFLD risk: evidence from U.S. and Korean national cohorts.","authors":"Yanxuan Zhong, Yanqi Kou, Zhuoyan Lu, Yujie Huang, Wanyi Yin, Qing Zhang, Zebin Wang, Shengyi Li, Bangna Du, Xiaole Li, Enhua Wu, Shicai Ye, Yuping Yang","doi":"10.1186/s12986-026-01162-9","DOIUrl":"10.1186/s12986-026-01162-9","url":null,"abstract":"<p><strong>Background: </strong>Nonalcoholic fatty liver disease (NAFLD), now redefined as metabolic dysfunction-associated steatotic liver disease (MASLD), affects 25-30% of adults globally and is driven by metabolic dysregulation. Concurrently, prolonged work hours and insufficient sleep are increasingly prevalent, yet their combined relationship with NAFLD risk remains unexplored. The Work-to-Sleep Ratio (WSR), quantifying the balance between occupational time and sleep recovery, may serve as a novel behavioral marker of NAFLD risk. Unlike work hours or sleep duration alone, WSR integrates these two interdependent behaviors into a single metric, capturing the balance between occupational demand and physiological recovery.</p><p><strong>Methods: </strong>This cross-sectional study utilized nationally representative data from the U.S. NHANES (2017-2023; n = 3,935) and Korean KNHANES (2019-2020 and 2022-2023; n = 10,729) cohorts. Multivariable logistic regression models with sequential covariate adjustment were employed to examine WSR-NAFLD associations. Restricted cubic spline analyses explored nonlinear relationships, while mediation analyses examined the potential involvement of adiposity (BMI), inflammation (CRP), and dyslipidemia (NHHR). Subgroup analyses assessed effect modification by demographic and clinical factors.</p><p><strong>Results: </strong>WSR exhibited nonlinear associations with NAFLD risk in both cohorts. In NHANES, NAFLD risk increased with rising WSR and attenuated at higher levels. In contrast, in KNHANES, higher WSR was associated with progressively increased NAFLD risk that plateaued at elevated ratios. Associations were stronger and more consistent in KNHANES (fully adjusted OR per unit increase in WSR 1.57, 95% CI 1.38-1.78). Subgroup analyses revealed stronger associations in younger adults and metabolically vulnerable groups. Mediation analyses identified adiposity (BMI) as accounting for the largest proportion of the observed WSR-NAFLD association, with secondary roles for inflammation (CRP) and dyslipidemia (NHHR).</p><p><strong>Conclusion: </strong>WSR may serve as a useful behavior-based marker associated with NAFLD in nationally representative U.S. and Korean cohorts, with associations most evident among younger adults. Adiposity appeared to play a central role in this association, with additional contributions from inflammation and dyslipidemia. These findings highlight WSR as a simple time-based indicator for identifying populations at elevated NAFLD risk. Longitudinal studies are needed to confirm these associations and clarify temporal relationships.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520681","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":"Low vitamin D status and cardiometabolic trait clustering in a primary-care adult cohort: association analysis and exploratory explainable machine-learning classification.","authors":"Boshra Mozaffar, Saleh A Alsanie, Fauzia Ashfaq, Nahlah Jaber Madkhali, Bayan F Alshahrani, Mohd Faheem Khan, Mohammad Idreesh Khan","doi":"10.1186/s12986-026-01174-5","DOIUrl":"10.1186/s12986-026-01174-5","url":null,"abstract":"<p><strong>Background: </strong>Low serum 25-hydroxyvitamin D (25(OH)D) commonly co-exists with obesity and adverse cardiometabolic traits. However, its cross-sectional association with dyslipidaemia, body composition and glycaemic markers in primary-care adults remains incompletely characterised. This study examined these associations as the primary objective and, as a secondary exploratory objective, assessed whether routine clinical variables could classify concurrent vitamin D deficiency using interpretable machine-learning models.</p><p><strong>Methods: </strong>In this cross-sectional study, adults attending routine health check-up services underwent anthropometric and body-composition assessment (BMI, body fat mass, body fat percentage and lean mass), metabolic-profile screening and vitamin-status assessment. Vitamin D status was classified as deficient (< 20 ng/mL), insufficient (20-29.9 ng/mL) or sufficient (≥ 30 ng/mL). Group comparisons, correlation analyses and multivariable regression models were performed. In a secondary exploratory analysis, logistic-regression and random-forest models were used to classify vitamin D deficiency from routine clinical variables after internal cross-validation.</p><p><strong>Results: </strong>In the overall analytic sample, the mean serum 25(OH)D level was 20.3 ± 8.0 ng/mL, and 50.3% of participants were obese. Vitamin D deficiency was associated with significantly higher BMI, body fat mass, body fat percentage, fasting blood glucose, HbA1c, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG) and TG-derived very-low-density lipoprotein cholesterol (VLDL-c) and with significantly lower high-density lipoprotein cholesterol (HDL-c) (all p < 0.05). Serum 25(OH)D was inversely correlated with adiposity indices and TG and positively correlated with HDL-c. In the secondary exploratory classification analysis, the dimension-reduced random-forest model showed higher internal discrimination than logistic regression for classifying vitamin D deficiency in this dataset.</p><p><strong>Conclusions: </strong>Primary-care cohort with a high obesity burden, lower vitamin D status was associated with greater adiposity, less favourable glycaemic indices and a more atherogenic lipid profile. The exploratory machine-learning analysis suggests that routine nutritional, body-composition and biochemical variables may help classify concurrent vitamin D deficiency. However, these findings require external validation and should not be interpreted as evidence of causality or immediate clinical utility.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472047","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":"Ketosis elevates plasma concentrations of D-β-hydroxybutyryl-phenylalanine (BHB-Phe) in humans.","authors":"Mette Glavind Bülow Pedersen, Emaan Ghias, Maj Bangshaab, Thien Vinh Loung, Mads Bisgaard Bengtsen, Mads Vandsted Svart, Esben Søndergaard, Lars Christian Gormsen, Niels Møller, Mogens Johannsen, Nikolaj Rittig","doi":"10.1186/s12986-026-01172-7","DOIUrl":"10.1186/s12986-026-01172-7","url":null,"abstract":"<p><strong>Introduction: </strong>β-hydroxybutyrate (BHB), produced during ketosis, can conjugate with amino acids forming BHB-amino acids. D-BHB-phenylalanine (D-BHB-Phe) is the most abundant BHB-amino acid and has been shown to reduce appetite and induce weight loss in mice, but its function and regulation in humans remain unclear. The objective of this study was to determine whether D-BHB-Phe concentrations vary across different degrees and forms of ketosis in humans.</p><p><strong>Methods: </strong>Plasma D-BHB-Phe was measured in samples from four clinical cross-over trials (i) after 21 days on a ketogenic diet (n = 10), (ii) after oral consumption of 30 g ketone salt (KS) and 30 g ketone ester (KE) (n = 14), (iii) after oral KE at doses of 10, 20 and 40 g (n = 10) and (iv) after oral versus intravenous KS administration (n = 8).</p><p><strong>Results: </strong>After 21 days of ketogenic dieting, plasma D-BHB-Phe became detectable (median 2.1 nmol/L; range 0.9-19.9), compared with near-undetectable concentrations during the standard diet (median 0; range 0-0.9; p = 0.005). Oral KS and KE increased D-BHB-Phe compared with placebo (intervention x time, p < 0.001). D-BHB-Phe rose dose-dependently after 10 g, 20 g, and 40 g of KE (intervention x time, p < 0.001). Oral KS induced higher peak concentrations of D-BHB-Phe (15.6 ± 6.4 nmol/L) compared with iso-ketotic intravenous KS infusion, which elicited only a modest peak (1.5 ± 0.3 nmol/L; intervention x time, p < 0.001). A positive association between the D-BHB and D-BHB-Phe concentration was observed in pooled analyses but was not consistent across cohorts.</p><p><strong>Conclusion: </strong>D-BHB-Phe is inducible by ketosis in humans. Our findings suggest involvement of the splanchnic bed in its production and support further exploration of D-BHB-Phe's role in appetite regulation and metabolic health.</p><p><strong>Clinical trial registrations: </strong>NCT05012748, NCT03935841, NCT05263401, NCT05581043.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456267","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":"Comparative efficacy of dietary patterns on glycemic and liver enzymes in metabolic dysfunction-associated steatotic liver disease: a network meta-analysis.","authors":"Vali Musazadeh, Amir Hossein Faghfouri, Mehrnaz Morvaridi, Mostafa Shahraki Jazinaki, Mahsa Mahmoudinezhad, Sanaz Barazandeh, Farzad Shidfar","doi":"10.1186/s12986-026-01161-w","DOIUrl":"https://doi.org/10.1186/s12986-026-01161-w","url":null,"abstract":"<p><strong>Background: </strong>Insulin resistance and hepatic dysfunction are strongly associated with metabolic dysfunction-associated steatotic liver disease (MASLD). Non-pharmacological approaches, particularly dietary interventions, have demonstrated considerable potential for mitigating these conditions.</p><p><strong>Objectives: </strong>In this network meta-analysis (NMA), we compared the relative efficacy of different dietary patterns on glycemic regulation and hepatic enzyme profiles.</p><p><strong>Methods: </strong>A comprehensive systematic search of PubMed, Scopus, Web of Science, Cochrane, and Google Scholar was conducted from inception to March 2025. The NMA was carried out based on both direct and indirect comparisons using random-effects models.</p><p><strong>Results: </strong>Pooled analysis on 25 RCTs showed that DASH diet was more effective in reducing HOMA-IR (MD = -0.60; 95% CI: -1.14, -0.05; P-scores = 0.76; p = 0.03), AST (MD = -4.99; 95% CI: -8.76, -1.21; P-scores = 0.23; p = 0.009), compared to placebo. Low-Glycemic-Index Mediterranean Diet (LGIMD) approach led to a statistically significant but not clinically meaningful decrease in A1C levels compared to the placebo (MD = -0.01%; 95% CI: -0.01, -0.005; P-scores = 0.42; p < 0.001). The Mediterranean diet (MD) significantly reduced ALT levels compared with placebo (MD = -10.21; 95% CI: -20.22 to -0.20; p = 0.04; P-score = 0.70).</p><p><strong>Conclusion: </strong>The present NMA indicates that dietary interventions, including the Mediterranean diet, DASH, and certain low-glycemic approaches, are effective strategies for the management of MASLD. However, a LGIMD has shown mixed glycemic effects (reduction in A1c but increase in HOMA-IR), which warrant careful interpretation and further investigation.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437302","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":"γ-GC mitigates MASLD by reducing CD36 palmitoylation and plasma membrane translocation mediated by AKT/KLF10/zDHHC7 axis.","authors":"Jinyi Zhou, Chen Yang, Yangyu Guo, Lishuang Zhao, Shuai Lu, Lan Luo, Da Zhou, Zhimin Yin","doi":"10.1186/s12986-026-01173-6","DOIUrl":"10.1186/s12986-026-01173-6","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a worldwide disease characterized by hepatic steatosis. γ-glutamylcysteine (γ-GC), a non-protein thiol peptide with nontoxic side effects, can alleviate insulin resistance (IR) and alcoholic liver disease (ALD). However, the role of γ-GC in MASLD remains elusive. Herein, the aim of this study was to reveal the effects and underlying molecular mechanisms of γ-GC in the progression of MASLD.</p><p><strong>Methods: </strong>In vivo model of mice fed with high-fat diet (HFD) and in vitro model of hepatocytes treated with FFA (oleic acid/palmitic acid = 2/1) were established to examine the therapeutic effects and molecular mechanisms of γ-GC in MASLD.</p><p><strong>Results: </strong>HFD mice develop dyslipidemia and hepatic steatosis due to obesity. Increased lipogenesis-related protein expression and aggravated fatty acid uptake are also observed in hepatocytes treated with FFA. Mechanistic studies suggest that γ-GC can alleviate hepatic lipid deposition and steatosis through balancing lipid metabolism. Importantly, γ-GC inhibits KLF10-regulated zDHHC7 transcription via activating AKT signaling, thereby suppressing zDHHC7-mediated CD36 palmitoylation and plasma membrane translocation. Ultimately, γ-GC reduces CD36-mediated fatty acid uptake and attenuates FFA-associated lipogenic signaling, resulting in the amelioration of MASLD.</p><p><strong>Conclusions: </strong>In summary, our results support γ-GC as a candidate dipeptide for the treatment of MASLD, which alleviates hepatic lipid deposition and steatosis by inhibiting KLF10/zDHHC7-mediated CD36 palmitoylation and plasma membrane translocation through activation of AKT signaling.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430915","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}