npj Metabolic Health and Disease最新文献_第3页

Will predictive AI make discovery research in metabolism obsolete. 预测性人工智能会使新陈代谢方面的发现研究过时吗？

npj Metabolic Health and Disease Pub Date : 2026-07-01 DOI: 10.1038/s44324-026-00117-1

Jingyu Sun, Syed Murtuza Baker, Magdalene K Montgomery, Hongpeng Zhou

引用次数: 0

CD59 drives diet-induced obesity and glucose intolerance, insulin resistance, and metabolic dysfunction-associated steatotic liver disease. CD59驱动饮食诱导的肥胖、葡萄糖耐受不良、胰岛素抵抗和代谢功能障碍相关的脂肪变性肝病。

npj Metabolic Health and Disease Pub Date : 2026-06-17 DOI: 10.1038/s44324-026-00115-3

Marian Zeibak, Netanel Karbian, Yael Riahi, Saja Baraghithy, Labiba Ahmad, Adi Tabib, Ifat Abromovitz, Bella Agranovitz, Hadar Benyamini, Eyal Gottlieb, Joseph Tam, Yuval Dor, Gil Leibowitz, Dror Mevorach

{"title":"CD59 drives diet-induced obesity and glucose intolerance, insulin resistance, and metabolic dysfunction-associated steatotic liver disease.","authors":"Marian Zeibak, Netanel Karbian, Yael Riahi, Saja Baraghithy, Labiba Ahmad, Adi Tabib, Ifat Abromovitz, Bella Agranovitz, Hadar Benyamini, Eyal Gottlieb, Joseph Tam, Yuval Dor, Gil Leibowitz, Dror Mevorach","doi":"10.1038/s44324-026-00115-3","DOIUrl":"10.1038/s44324-026-00115-3","url":null,"abstract":"CD59 is known as a membrane-bound regulator of the complement system that prevents the formation of the membrane attack complex on host cells. Here we report the metabolic consequences of CD59a knockout (KO) in mice fed a high-fat diet (HFD). Mice lacking CD59a were protected from the development of insulin resistance, glucose intolerance, hyperinsulinemia, obesity, and fatty liver. Mutants fed an HFD had elevated adiponectin levels and reduced leptin levels in plasma. Data from metabolic cages suggested decreased appetite and an increase in voluntary wheel activity in mutants. Liver transcriptome analysis showed a marked decrease of inflammatory and fibrotic pathways in CD59a KO mice on an HFD, and plasma and liver metabolomics were remarkably similar, indicating close correspondence between systemic and hepatic metabolic profiles. In conclusion, we uncover a noncanonical role of CD59a in the development of diet-induced insulin resistance, hyperinsulinemia, glucose intolerance, and obesity.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13276272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148274434","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}

引用次数: 0

Ultra-processed foods and cardiometabolic risk: from evidence to policy. 超加工食品与心脏代谢风险：从证据到政策。

npj Metabolic Health and Disease Pub Date : 2026-06-02 DOI: 10.1038/s44324-026-00116-2

Hayley M O'Neill

引用次数: 0

An oral tyrosine challenge test for functional phenotyping of microbiota-derived phenyl sulfate production. 一种用于微生物源性硫酸苯生产功能表型的口服酪氨酸激发试验。

npj Metabolic Health and Disease Pub Date : 2026-06-02 DOI: 10.1038/s44324-026-00114-4

Ting-Yun Lin, Szu-Chun Hung, Takaaki Abe

{"title":"An oral tyrosine challenge test for functional phenotyping of microbiota-derived phenyl sulfate production.","authors":"Ting-Yun Lin, Szu-Chun Hung, Takaaki Abe","doi":"10.1038/s44324-026-00114-4","DOIUrl":"10.1038/s44324-026-00114-4","url":null,"abstract":"Phenyl sulfate (PS), a gut microbiota-derived metabolite implicated in the pathogenesis of diabetic kidney disease, is generated through microbial conversion of dietary tyrosine to phenol, followed by hepatic sulfation via SULT1A1. We developed an oral tyrosine challenge test (OTyCT) to phenotype individual PS-producing capacity. Forty-eight healthy adults underwent a standardized tyrosine load with serial plasma PS levels measured over 48 h using LC-MS. OTyCT revealed substantial interindividual variability of PS production independent of baseline PS levels, highlighting marked heterogeneity in host-microbiome metabolic interactions. Sixteen participants in the highest tertile of the incremental area under the curve of PS were defined as high-PS producers. High PS producers exhibited distinct gut microbial signatures despite comparable abundances of known phenol-biosynthetic genes and host SULT1A1 genotypes. These findings suggest that susceptibility to PS-related complications may vary according to gut microbial profiles, supporting OTyCT as a practical tool for metabolic phenotyping and microbiome-informed precision nutrition. Clinical Trial registry name and registration number: Identification of P-Cresyl Sulfate Producer Phenotype by Oral Tyrosine Challenge Test: Interactions Among Diet, Gut Microbiota, and Host Genome, NCT04204174.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13230720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148152947","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}

引用次数: 0

snRNA-seq identifies Fmo2⁺ fibroblasts as drivers of hyperglycemic memory-induced cardiac injury. snRNA-seq鉴定Fmo2+成纤维细胞是高血糖记忆诱导的心脏损伤的驱动因素。

npj Metabolic Health and Disease Pub Date : 2026-05-27 DOI: 10.1038/s44324-026-00113-5

Shihan Xu, Chunxiao Ju, Mengmeng Zhu, Yajie Cai, Fengqin Xu, Yanfei Liu, Yue Liu

{"title":"snRNA-seq identifies Fmo2+ fibroblasts as drivers of hyperglycemic memory-induced cardiac injury.","authors":"Shihan Xu, Chunxiao Ju, Mengmeng Zhu, Yajie Cai, Fengqin Xu, Yanfei Liu, Yue Liu","doi":"10.1038/s44324-026-00113-5","DOIUrl":"10.1038/s44324-026-00113-5","url":null,"abstract":"Despite intensive glycemic control, diabetic cardiomyopathy (DCM) often progresses due to hyperglycemic memory (HGM), yet the specific cardiac cells perpetuating this injury remain unknown. To address this, we performed single-nucleus RNA sequencing (snRNA-seq) on hearts from an HGM rat model. Our analysis of 86,120 nuclei revealed HGM-specific inflammatory and epigenetic reprogramming signatures. Fibroblasts emerged as potential mediators, appearing to drive extracellular matrix remodeling via upregulated LAMININ and COLLAGEN signaling. We uncovered a distinct HGM-specific fibroblast subpopulation characterized by oxidative stress and H3K27 demethylation. Integrative analysis prioritized Fmo2 as a key pathogenic candidate, which was further supported via Mendelian randomization and clinical data as a putative causal gene. This study suggests that a pathogenic Fmo2+ fibroblast subpopulation may act as a pathological \"memory carrier,\" providing novel mechanistic insights and proposing exploratory therapeutic avenues for HGM-induced cardiac damage beyond glycemic control.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13216310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148045302","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}

引用次数: 0

Restoring mitochondrial health after blast-induced traumatic brain injury: modifiable factors and therapeutic opportunities. 在爆炸诱导的创伤性脑损伤后恢复线粒体健康：可改变的因素和治疗机会。

npj Metabolic Health and Disease Pub Date : 2026-05-13 DOI: 10.1038/s44324-026-00111-7

Cortney J Laye, W Brad Hubbard

{"title":"Restoring mitochondrial health after blast-induced traumatic brain injury: modifiable factors and therapeutic opportunities.","authors":"Cortney J Laye, W Brad Hubbard","doi":"10.1038/s44324-026-00111-7","DOIUrl":"10.1038/s44324-026-00111-7","url":null,"abstract":"Blast-induced traumatic brain injury (blast TBI) causes diffuse neuropathology, blood-brain barrier disruption, and complex neurological sequelae. Mitochondrial dysfunction is increasingly recognized as a contributor to secondary injury cascades and has been associated with bioenergetic impairment, alterations in mitochondrial dynamics, oxidative stress, and apoptotic signaling following blast exposure. Primary data from our recent study demonstrates acute TCA cycle impairment and supports a framework of glycolytic shift in the brain alongside a bottleneck of key TCA cycle intermediates. This review also examines current literature on mitochondrial pathophysiology across neurons, astrocytes, and endothelial cells after blast TBI. We highlight cumulative data detailing disruptions in mitochondrial quality control, including fission-fusion imbalance, and altered mitophagy, as well as bioenergetic dysfunction, calcium dysregulation, enzymatic alterations, and oxidative damage. The influence of lifestyle and environmental modifiers on brain mitochondrial health and how it can alter long-term outcomes after blast TBI are also discussed. We further discuss therapeutic strategies, including mild mitochondrial uncouplers, modulators of mitochondrial dynamics, and mitochondrial transplantation, aimed at preserving mitochondrial integrity and function. Collectively, these findings demonstrate that mitochondrial dysfunction is an important component of blast TBI pathophysiology and supports continued investigation of approaches that integrate modifying factors and therapeutic strategies to improve outcomes after blast TBI.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13172328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936771","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}

引用次数: 0

Reply to: Concerns regarding interpretation and reporting in Kolivas et al. mHealth low carbohydrate dietary intervention in T2D. 回复：对Kolivas等mHealth对T2D低碳水化合物饮食干预的解释和报告的关注。

npj Metabolic Health and Disease Pub Date : 2026-04-24 DOI: 10.1038/s44324-026-00104-6

Despina Kolivas, George Moschonis

引用次数: 0

Concerns regarding interpretation and reporting in Kolivas et al. mHealth low carbohydrate dietary intervention in T2D. 对Kolivas等mHealth低碳水化合物饮食干预T2D的解释和报告的关注。

npj Metabolic Health and Disease Pub Date : 2026-04-24 DOI: 10.1038/s44324-026-00105-5

J Dening

引用次数: 0

Lipid membrane remodeling by myristic acid treatment reverses Parkinson's disease α-synuclein phenotypes in patient neurons. 肉豆蔻酸治疗脂膜重塑可逆转帕金森病患者神经元α-突触核蛋白表型。

npj Metabolic Health and Disease Pub Date : 2026-04-14 DOI: 10.1038/s44324-026-00110-8

Julian Avila Pacheco, Gleidia Sauli, Luis Fonseca-Ornelas, Haley Cirka, Deepa Kumari, Morgan Hazo, Sarah Jeanfavre, Pedro H Vendramini, Christina R Muratore, Clary B Clish, Dennis Selkoe, Saranna Fanning

{"title":"Lipid membrane remodeling by myristic acid treatment reverses Parkinson's disease α-synuclein phenotypes in patient neurons.","authors":"Julian Avila Pacheco, Gleidia Sauli, Luis Fonseca-Ornelas, Haley Cirka, Deepa Kumari, Morgan Hazo, Sarah Jeanfavre, Pedro H Vendramini, Christina R Muratore, Clary B Clish, Dennis Selkoe, Saranna Fanning","doi":"10.1038/s44324-026-00110-8","DOIUrl":"10.1038/s44324-026-00110-8","url":null,"abstract":"Despite the lipid-rich nature of the brain, defining the role of lipid metabolism in neurodegenerative disease and targeting lipid metabolic pathways for disease modification are in their infancy. In Parkinson's disease, Lewy body dementia, and other synucleinopathies, disease-associated forms of α-synuclein (αS) alter fatty acid (FA) metabolism, increasing monounsaturated FA-containing lipids. This disequilibrium in membrane fatty acyl composition results in aberrant αS:membrane interactions. We report treating PD patient neurons with myristic acid (C14:0) induces lipid metabolism modifications correcting abnormal PD-associated membrane composition and reversing PD-relevant phenotypes. C14:0 conditioning reduced Lewy-like αS inclusions; reduced abnormal pSer129 αS; corrected excess αS at membranes; and restored native αS tetramer:monomer homeostasis. Using nuclear magnetic resonance, we established C14:0 as correcting abnormal αS vesicle membranes dwell time in vitro, correlating with less pathogenic αS aggregation. Mechanistically, C14:0 rescued PD neuron phenotypes through remodeling the PD-associated lipidome, eliciting beneficial effects by increasing shorter, saturated fatty acyl-lipids.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694314","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}

引用次数: 0

Beta 2 adrenergic receptor agonists as a treatment for metabolic dysfunction-associated steatohepatitis (MASH). β 2肾上腺素能受体激动剂治疗代谢功能障碍相关脂肪性肝炎（MASH）。

npj Metabolic Health and Disease Pub Date : 2026-03-25 DOI: 10.1038/s44324-026-00108-2

Brennan S Winkler, Kristina M Stayer, Abhinav K Rao, Ehtesham Arif, Tsultrim T Mendenhall, Kristy L Thomas, Kylie R Driggers, Xiaofeng Zuo, Wayne Fitzgibbon, Peifeng Deng, Yanhui Su, Yujing Dang, Marie Gerges, Daniel Kagan, Vishwajeeth Pasham, Bethany Wolf, Don C Rockey, Jessica H Hartman, Joshua H Lipschutz

{"title":"Beta 2 adrenergic receptor agonists as a treatment for metabolic dysfunction-associated steatohepatitis (MASH).","authors":"Brennan S Winkler, Kristina M Stayer, Abhinav K Rao, Ehtesham Arif, Tsultrim T Mendenhall, Kristy L Thomas, Kylie R Driggers, Xiaofeng Zuo, Wayne Fitzgibbon, Peifeng Deng, Yanhui Su, Yujing Dang, Marie Gerges, Daniel Kagan, Vishwajeeth Pasham, Bethany Wolf, Don C Rockey, Jessica H Hartman, Joshua H Lipschutz","doi":"10.1038/s44324-026-00108-2","DOIUrl":"10.1038/s44324-026-00108-2","url":null,"abstract":"MASH is a leading cause of liver transplantation. Here, we investigated formoterol, a long-acting β2 adrenergic receptor agonist (LABA), in MASH. Mice treated with a high-fat diet (HFD) for sixteen weeks developed liver steatosis and were treated with formoterol or vehicle for four weeks. Steatosis largely resolved following formoterol treatment. To investigate mechanism, we evaluated mitochondrial biogenesis and found in HFD mice treated with formoterol versus vehicle that: PGC1α levels and electron transport chain components were significantly higher; mitochondrial number was increased; and lipids were decreased. Human HepaRG liver cells were then exposed to free fatty acids and/or formoterol. Formoterol attenuated lipid accumulation and increased ATP-linked basal and maximal respiration. Finally, a retrospective analysis of 59,644 patients with MASH showed that patients taking LABAs had fewer complications of advanced liver disease and lower mortality. Together, these data raise the possibility that LABAs, especially formoterol, could be a novel MASH treatment.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13018619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518062","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}

引用次数: 0