Nutrition & Metabolism最新文献

{"title":"Response of FTO gene polymorphisms to continuous caloric restriction diets on lipid and glycemic biomarkers in overweight and obese adults: a systematic review and meta-analysis.","authors":"Tran Quang Duc, Nguyen Di Khanh, Dang Dang Khoa, Nguyen Huynh Phuong Anh","doi":"10.1186/s12986-026-01171-8","DOIUrl":"10.1186/s12986-026-01171-8","url":null,"abstract":"<p><strong>Background: </strong>Common variants in the fat mass and obesity-associated (FTO) gene are linked to obesity and cardiometabolic risk, but whether they modify lipid and glycemic responses to continuous energy restriction (CER) remains unclear. We evaluated genotype-specific changes in lipid and glycemic biomarkers following CER-based dietary interventions in adults with overweight/obesity.</p><p><strong>Methods: </strong>A literature search of four databases identified eligible intervention trials published through March 2026. Results were synthesized using random-effects meta-analyses, reporting mean differences (MDs) with 95% confidence intervals (CI). Subgroup analyses and sensitivity analyses were conducted, and the certainty of evidence was assessed.</p><p><strong>Results: </strong>Fifteen articles (18 effect sizes for lipid outcomes; 21 for glycemic outcomes; 4,941 participants). Compared with non-carriers, FTO risk-allele carriers had higher triglycerides (MD 5.98 mg/dL; 95% CI 1.03 to 10.93). No significant genotype-related differences were observed for total cholesterol, LDL-C, HDL-C, fasting glucose, insulin, or HOMA-IR, and all sensitivity analyses were consistent with these findings. Subgroup tests showed no significant differences by intervention duration, study design or genotype model. Genotype-contrast analyses suggested differences in triglycerides and LDL-C (higher TG in AA carriers and greater LDL-C reduction in AA carriers) and in fasting glucose (greater reduction in AT/AA carriers) compared with non-carriers. Overall certainty of evidence ranged from low to very low (GRADE).</p><p><strong>Conclusions: </strong>Most lipid and glycemic markers were comparable across FTO genotypes during CER, whereas triglycerides were higher in risk-allele carriers. Replication in prospective trials with pre-specified genetic stratification is needed before these findings can inform clinical practice.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369188","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":"Vitamin E administration reduces liver enzyme levels in patients with Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD): evidence from a systematic review and meta-analysis.","authors":"Mehdi Karimi, Maryam Abidi, Ramak Gholamian, Alireza Ostovan, Negar Zakerolhosseini, Sara Boroomand, Sana Esmaeili, Mohammad Hadi Pourramezan, Sina Mohebi, Abolfazl Javadimoghadam, Farimah Behmaneshnia, Omid Asbaghi","doi":"10.1186/s12986-026-01158-5","DOIUrl":"10.1186/s12986-026-01158-5","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent and frequently associated with elevated liver enzymes, indicating hepatic injury. Although vitamin E has been investigated as a therapeutic antioxidant, its effects on liver enzyme levels remain inconsistent. This study aims to systematically review and quantitatively synthesize the evidence of the effects of vitamin E administration on liver enzymes in patients with MASLD.</p><p><strong>Methods: </strong>A systematic search of scientific databases was conducted up to September 2025 to identify relevant randomized clinical trials (RCTs). Data on alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) were extracted. Pooled effect sizes were calculated as weighted mean differences (WMD) with 95% confidence intervals (CIs) using a random-effects model.</p><p><strong>Results: </strong>The pooled analysis of 16 RCTs (22 effect sizes) showed that vitamin E administration significantly reduced serum liver enzyme levels in patients with MASLD, including AST (WMD: -5.94 IU/L), ALT (WMD: -7.33 IU/L), ALP (WMD: -5.68 IU/L), and GGT (WMD: -5.54 IU/L), all with statistical significance (p ≤ 0.008). Subgroup analyses revealed that longer intervention durations and higher vitamin E doses were generally associated with greater improvements in liver enzyme levels, particularly AST and ALT. In contrast, Significant reductions in ALP were mainly observed in shorter trials and with lower vitamin E doses, especially at higher doses and among obese populations. Overall, benefits were consistent across BMI categories, though effects appeared more pronounced in obese individuals.</p><p><strong>Conclusion: </strong>Vitamin E supplementation was associated with significant reductions in serum liver enzymes, suggesting improvement in hepatocellular injury and necroinflammatory activity in patients with MASLD. However, the available evidence is insufficient to determine its effects on fibrosis progression, metabolic burden, or long-term liver-related outcomes.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352699","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":"Exosomal miRNA-714 derived from adipose tissue macrophages regulates adipocyte glucose and lipid metabolism via IGF1R targeting.","authors":"Rui Ma, Lei Li, Jing Yang, Sheng Jiang","doi":"10.1186/s12986-026-01153-w","DOIUrl":"10.1186/s12986-026-01153-w","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to elucidate the regulatory role and underlying molecular mechanisms of exosomal microRNA (miR)-714, derived from adipose tissue macrophages (ATMs), in modulating glucose and lipid metabolism in adipocytes. The findings may contribute to the identification of novel therapeutic targets for obesity-related metabolic disorders.</p><p><strong>Methods: </strong>Differentially expressed miRNAs and their corresponding target genes were identified through bioinformatics analyses using publicly available datasets. An obesity model was induced in mice via high-fat diet (HFD) administration to evaluate parameters such as body weight, blood glucose levels, and the expression of miR-714 and insulin-like growth factor 1 receptor (IGF1R) in ATM-derived exosomes. Cultured 3T3-L1 adipocytes were used for in vitro analyses. Target gene validation was conducted using dual-luciferase reporter assays. Glucose consumption, triglyceride (TG) content, and the expression of relevant metabolic genes were also measured.</p><p><strong>Results: </strong>High-throughput analysis demonstrated a significant upregulation of miR-714 in ATM-derived exosomes from obese mice, accompanied by a downregulation of IGF1R expression in adipose tissue. In vivo findings confirmed elevated miR-714 levels in the HFD group, with a corresponding reduction in IGF1R protein levels. In vitro assays confirmed that the direct interaction between miR-714 and the 3' untranslated region (3'UTR) of Igf1r led to reduced Glucose consumption by adipocytes (reflected as increased glucose concentration in the culture supernatant), intracellular TG accumulation, and reduced IGF1R protein expression.</p><p><strong>Conclusion: </strong>Exosomal miR-714 secreted by ATMs impairs Glucose consumption and promotes TG accumulation in adipocytes by downregulating IGF1R expression, thereby impairing Glucose consumption and promoting TG accumulation in adipocytes. These findings highlight the critical role of the miR-714/IGF1R axis in adipocyte metabolic regulation and provide a theoretical basis for non-invasive diagnostic strategies and targeted therapies for obesity-related metabolic conditions.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302435","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":"Impact of L-carnitine supplementation on lipid profile parameters in overweight and obese women: a systematic review and meta-analysis of randomized controlled trials.","authors":"Yongmei Yu, Dongping Xu, Siyi Shang, Yuanxia Liu, Zhengxian Qian","doi":"10.1186/s12986-026-01159-4","DOIUrl":"10.1186/s12986-026-01159-4","url":null,"abstract":"<p><strong>Background and aim: </strong>L-carnitine plays a central role in fatty acid metabolism and has been proposed as a potential strategy for improving lipid regulation. However, evidence from clinical trials remains inconsistent, and female-specific data are scarce. This systematic review and meta-analysis aimed to evaluate the effects of L-carnitine supplementation on lipid profiles specifically in women with overweight or obesity.</p><p><strong>Methods: </strong>A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted in accordance with PRISMA guidelines. Eligible studies enrolled women with BMI ≥ 25 kg/m² and compared L-carnitine supplementation with placebo or no intervention. Pooled weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model.</p><p><strong>Results: </strong>Ten RCTs were included. L-carnitine supplementation significantly reduced TG (WMD: - 8.01 mg/dL; 95%CI: - 15.21 to - 0.81), TC (WMD: - 7.85 mg/dL; 95%CI: - 14.54 to - 1.16), and LDL-C (WMD: - 5.59 mg/dL;95%CI: - 10.02 to - 1.16). No significant overall effect was found for HDL-C (WMD:1.09 mg/dL;95%CI: - 1.79 to 3.99). Subgroup analyses indicated stronger effects at higher doses, shorter intervention durations, and in participants with elevated baseline lipid levels.</p><p><strong>Conclusion: </strong>L-carnitine supplementation provides significant improvements in TG, TC, and LDL-C among overweight and obese women, although HDL-C responses remain inconsistent. These findings suggest a potential adjunctive role for L-carnitine in cardiometabolic risk management.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302459","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":"Integrating epidemiological and transcriptomic data reveals novel lipid metabolic drivers of obstructive sleep apnea.","authors":"Yanhui Liu, Sisi Gong, Jiaqi Wang, Shanshan Chen, Yiming Zeng, Chunmei Fan","doi":"10.1186/s12986-026-01160-x","DOIUrl":"10.1186/s12986-026-01160-x","url":null,"abstract":"<p><strong>Background: </strong>Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep and is frequently accompanied by dyslipidemia. However, the molecular mechanisms linking lipid metabolism to OSA remain incompletely understood. This study aimed to investigate the association between blood lipid levels and OSA and explore potential underlying molecular pathways.</p><p><strong>Methods: </strong>Data from the National Health and Nutrition Examination Survey (NHANES) 2005-2008 and 2015-2018 were analyzed to evaluate the associations between OSA and blood lipid parameters using multivariable regression and sensitivity analyses. Additionally, OSA-related transcriptomic data (GSE135917) were obtained from the Gene Expression Omnibus (GEO), and lipid metabolism-related genes were retrieved from the Molecular Signatures Database (MSigDB). Differentially expressed lipid metabolism-related genes (DELMRGs) were identified through data integration. Machine learning approaches, protein-protein interaction network analysis, and receiver operating characteristic analysis were applied to identify key genes. Gene set enrichment analysis (GSEA) was performed to elucidate associated biological pathways, and transcription factor-gene and gene-microRNA regulatory networks were constructed using NetworkAnalyst and Cytoscape.</p><p><strong>Results: </strong>Analysis of NHANES data showed that triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels were positively associated with OSA, whereas high-density lipoprotein cholesterol (HDL-C) levels was inversely associated (all p < 0.001). A nonlinear, inverted U-shaped association between TG levels and OSA risk was also observed (p for nonlinearity < 0.05). Transcriptomic analysis identified 34 DELMRGs, among which CYP3A4, CYP4A22, and MED18 emerged as key genes. GSEA revealed pathways potentially involved in lipid metabolism and OSA pathophysiology, while regulatory network analyses further supported the biological relevance of these genes.</p><p><strong>Conclusions: </strong>This study demonstrates that dyslipidemia characterized by elevated TG and LDL-C levels and reduced HDL-C levels is associated with an increased likelihood of OSA, and identifies three DELMRGs that may be involved in OSA pathophysiology. These findings provide exploratory mechanistic insights and offer a basis for future studies to further investigate the role of lipid metabolism in OSA.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295675","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":"Dietary index for gut microbiota, plasma metabolome, and risks of metabolic dysfunction-associated steatotic liver disease and other chronic liver diseases.","authors":"Mengyu Zhou, Yuqing Deng, Yuxiang Huang, Chao Yu, Xuechen Chen, Qiaoqiao Yang, Yingxin Liao, Shijia Wang, Peiting Zhang, Ailan Chen, Wenhua Ling, Xu Chen, Jiaying Li, Hongliang Xue","doi":"10.1186/s12986-026-01145-w","DOIUrl":"10.1186/s12986-026-01145-w","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The dietary index for gut microbiota (DI-GM) is a newly proposed metric for assessing diet quality linked to gut microbiota. However, prospective evidence is scarce on the associations between DI-GM and adverse liver outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The DI-GM was calculated by averaging the intakes of 12 foods and nutrients. Elastic net regression was performed to identify metabolites associated with DI-GM and metabolic signature reflecting higher adherence to DI-GM was constructed. Cox proportional hazards regression and mediation analyses were employed to explore the potential associations and mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;This prospective cohort study included 168,456 participants from the UK Biobank. Compared to participants with DI-GM scores of 0-3, those scoring ≥ 6 presented 22% lower risk of MASLD (HR = 0.78, 95% CI = 0.68-0.90). Metabolic signature for DI-GM and dietary index beneficial to gut microbiota (BDI-GM) were also inversely correlated with MASLD. Similar inverse correlations between DI-GM and BDI-GM and the risks of other chronic liver diseases were identified. Furthermore, phenotypic age, body mass index, metabolic score, inflammatory score, and metabolic signature significantly mediated the relationship between DI-GM and MASLD. No significant interactions were observed between DI-GM and polygenic risk score of hepatic steatosis, and the associations between DI-GM and adverse liver outcomes persisted regardless of genetic risk.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Higher adherence to DI-GM significantly correlates with reduced risks of MASLD and other chronic liver diseases, independent of genetic susceptibility. And the apparent mediating effects of five indices highlight the role of aging, obesity, metabolic disorders, inflammation, and metabolomic alterations in the association between DI-GM and MASLD. Further research is warranted to evaluate the utility of metabolic signatures in metabolic profile monitoring and risk stratification.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Impact and implications: &lt;/strong&gt;This large-scale cohort study first demonstrates that higher adherence to a gut microbiota-beneficial diet (DI-GM) is associated with a lower risk of MASLD and other chronic liver diseases, independent of genetic susceptibility. The estimated population attributable fractions, while derived from observational data and requiring cautious interpretation, suggest that a substantial portion of liver disease cases in the study population might be linked to suboptimal DI-GM adherence. These findings underscore the importance of integrating gut microbiome health into public health strategies for liver disease prevention, offering a practical approach to reduce disease burden at both individual and population levels. The DI-GM-associated metabolic signature represents a candidate objective biomarker meriting evaluation in future studies for its potential in early risk assessment. Mediation analyses fur","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283719","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":"Dietary protein, major dietary protein sources, and chronic joint diseases risk.","authors":"Yiqian Zhou, Chunlei He, Yihao Fan, Yun Hong, Shuhui Chen, Ding Ye, Xiaohui Sun, Jing Guo, Jiayu Li, Yingying Mao","doi":"10.1186/s12986-026-01140-1","DOIUrl":"10.1186/s12986-026-01140-1","url":null,"abstract":"<p><strong>Objectives: </strong>Evidence on dietary protein and chronic joint diseases remains limited. This study aimed to investigate the associations between protein intake and the risk of chronic joint diseases, and to evaluate the mediating roles of inflammation.</p><p><strong>Methods: </strong>Dietary protein intake was assessed using 24-hour dietary recall. The primary outcomes, including incident OA, RA, gout, and SpA, were ascertained from UK hospital inpatient records. Cox proportional hazards models estimated associations between protein intake and outcomes. Mediation analysis was conducted using the CMAverse R package.</p><p><strong>Results: </strong>During an average follow-up of 12.19-13.18 years, a total of 23,298 incident cases of OA, 2,070 of RA, 2,934 of gout, and 728 of SpA were documented. Higher total protein intake was associated with a reduced risk of gout (Q4 vs. Q1: HR:0.87, 95%CI 0.79-0.97), vegetable protein intake with lower risks of OA (0.89, 0.86-0.93) and RA (0.76, 0.67-0.87), whereas animal protein intake was related to an increased risk of OA (1.07, 1.03-1.12). Regarding protein-rich foods, whole grains, legumes and cheese intake were associated with lower OA risk. Whole grains, seafood, cheese, and yogurt were negatively associated with RA risk. And red meat was associated with increased RA risk. C-reactive protein was identified as a significant mediator for associations of vegetable and animal protein with OA risk, and of vegetable protein with RA risk.</p><p><strong>Conclusion: </strong>Higher total protein intake was linked to a lower risk of gout. Vegetable protein intake was associated with reduced risks of OA and RA, whereas animal protein intake was associated with an increased risk of OA.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13377832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272244","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":"Sarcopenic obesity in cirrhosis: prognostic value and future perspectives.","authors":"Yanhua Chen, Ziheng Liao, Cong Wang, Yuanyuan Zhang, Rui Huang","doi":"10.1186/s12986-026-01154-9","DOIUrl":"10.1186/s12986-026-01154-9","url":null,"abstract":"<p><p>Sarcopenic obesity (Sa-O) is an emerging prognostic factor in patients with cirrhosis, yet its diagnostic criteria and clinical significance remain incompletely defined. This narrative review synthesizes evidence from the past five years on the pathogenesis, diagnostic criteria, and prognostic implications of Sa-O in cirrhosis. Diagnostic criteria were categorized according to their definitions of sarcopenia and obesity, and the clinical utility of assessment tools was evaluated. Prognostic value was examined across seven clinical domains. Existing evidence indicates that Sa-O is associated with increased mortality and adverse post-transplant outcomes. Limited data suggest potential links with classic cirrhosis complications, while cardiovascular events remain underexplored as primary endpoints. Current studies on acute-on-chronic liver failure focus on sarcopenia or obesity in isolation rather than their coexistence. Health-related quality of life and the integration of Sa-O into established prognostic score models are rarely addressed. In summary, Sa-O should be recognized as a key prognostic factor in cirrhosis and represents a modifiable target for early lifestyle intervention.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265528","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":"Gut microbiota, brown adipose tissue whitening, and obesity: nutritional modulators and metabolic crosstalk.","authors":"Majid Ghodraty, Mehrshad Fekri, Maedeh Kiani, Sepehr Esmaeel Zadegan, Shailin Abdoli Rezaei, Seyedeh Sara Mousavi Gilani, Mahsa Manafi Varkiani, Atie Ghafouri, Nariman Mehrnia, Masume Amudi, Zahra Khodayar, Amir Jouya Talaei, Mohammad Baadkoubehazaveh","doi":"10.1186/s12986-026-01152-x","DOIUrl":"10.1186/s12986-026-01152-x","url":null,"abstract":"<p><p>Obesity reflects a chronic imbalance between energy intake and expenditure, accompanied by metabolic inflammation and ectopic lipid deposition. Accumulating evidence indicates that gut microbiota dysbiosis reshapes host nutrient handling and endocrine-immune signaling, with downstream consequences for thermogenic adipose tissues. Brown adipose tissue (BAT) supports energy dissipation via UCP1-dependent adaptive thermogenesis; however, in obesity, BAT often undergoes \"whitening,\" a maladaptive transition characterized by lipid accumulation, mitochondrial dysfunction, and reduced thermogenic capacity. This review synthesizes mechanistic and translational evidence linking obesity-associated microbiota alterations to BAT dysfunction through integrated gut-adipose and gut-liver communication. We discuss how microbially derived metabolites (including short-chain fatty acids and secondary bile acids), endotoxin-driven inflammation, and bile acid receptor signaling (FXR/TGR5) may converge on sympathetic tone, mitochondrial biogenesis, and lipid flux to favor BAT whitening. We further evaluate nutrition- and lifestyle-based strategies (dietary fiber and polyphenols, exercise, pre/pro/postbiotics, and bile acid-targeted approaches) that modulate microbial ecology and metabolic outputs, with potential to preserve BAT thermogenic identity and improve metabolic health. Clarifying the causal pathways and clinically actionable microbial signatures within this gut-adipose-liver network may inform future nutrition-oriented interventions for obesity and related metabolic disorders.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265559","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":"PDK4 drives time-dependent physical endurance impairment during acute hypoxia by disrupting carbohydrate metabolism.","authors":"Peng Wang, Yundong Xia, Min Zhou, Xin Rao, Shuping Mao, Hedong Lang, Long Yi, Mantian Mi","doi":"10.1186/s12986-026-01155-8","DOIUrl":"10.1186/s12986-026-01155-8","url":null,"abstract":"<p><strong>Background: </strong>Exposure to acute hypoxia severely impairs skeletal muscle function, but the temporal dynamics and underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>Male C57BL/6 mice were exposed to normobaric hypoxia (FiO₂ = 11.8%, simulating 4,500 m) for 0, 12, 24, 48, and 72 h. Exercise performance was evaluated through endurance and strength tests. Transcriptomic and metabolic adaptations were detected through RNA-seq and biochemical assays. Target validation was performed using adeno-associated virus (AAV) mediated gene knockdown and dichloroacetate (DCA).</p><p><strong>Results: </strong>Endurance was most severely impaired after 12 h of hypoxic exposure and showed a trend toward recovery by 72 h, whereas muscle strength declined progressively. Hypoxia induced a metabolic reprogramming favoring oxidative phosphorylation, coupled with a marked upregulation of PDK4 at 12 h. This was associated with increased pyruvate dehydrogenase (PDH) phosphorylation, favoring the diversion of pyruvate away from oxidation and contributing to lactate accumulation. Both DCA treatment and AAV-mediated PDK4 knockdown improved endurance performance under hypoxic conditions.</p><p><strong>Conclusion: </strong>These findings suggest that acute hypoxia impairs endurance, in part through PDK4-mediated alterations in pyruvate metabolism, providing a mechanistic basis for optimizing nutritional and therapeutic strategies under hypoxic stress.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265565","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}