Nature metabolism最新文献_第3页

Rare science, real impact: shaping the future of research on rare metabolic diseases 罕见的科学，真正的影响：塑造罕见代谢疾病研究的未来

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-09-23 DOI: 10.1038/s42255-026-01631-8

Anu Suomalainen, Ralph J. DeBerardinis, Julien Baruteau, Hélène Puccio, Takanobu Otomo, Marni J. Falk

引用次数: 0

Author Correction: N6-methyladenosine (m6A) in 18S rRNA promotes fatty acid metabolism and oncogenic transformation 作者更正：18S rRNA中的n6 -甲基腺苷（m6A）促进脂肪酸代谢和致癌转化

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-09-22 DOI: 10.1038/s42255-026-01637-2

Hao Peng, Binbin Chen, Wei Wei, Siyao Guo, Hui Han, Chunlong Yang, Jieyi Ma, Lu Wang, Sui Peng, Ming Kuang, Shuibin Lin

引用次数: 0

Gut microbiome maturation in early childhood interacts with host genetics to predict type 1 diabetes risk 儿童早期肠道微生物群成熟与宿主遗传相互作用预测1型糖尿病风险

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-09-21 DOI: 10.1038/s42255-026-01614-9

Danyue Dong, Aaron M. Walsh, Tommi Vatanen, George Weingart, Mondher Khdhiri, Meir J. Stampfer, Kendra Vehik, Eric A. Franzosa, Curtis Huttenhower, Dong D. Wang, The TEDDY Study Group

{"title":"Gut microbiome maturation in early childhood interacts with host genetics to predict type 1 diabetes risk","authors":"Danyue Dong, Aaron M. Walsh, Tommi Vatanen, George Weingart, Mondher Khdhiri, Meir J. Stampfer, Kendra Vehik, Eric A. Franzosa, Curtis Huttenhower, Dong D. Wang, The TEDDY Study Group","doi":"10.1038/s42255-026-01614-9","DOIUrl":"10.1038/s42255-026-01614-9","url":null,"abstract":"Prospective evidence linking early-life microbiome development and host genetics with type 1 diabetes (T1D) risk is limited. Here, we describe how gut microbiome maturation and host genetics influence T1D risk in the TEDDY study. We analysed 12,151 longitudinal metagenomes and host genetic data from 887 children at high genetic risk for T1D followed for up to 6 years. We identify three microbiome maturational patterns: Early Matured, Late Matured and Early Plateaued, driven primarily by non-linear changes in species from the Bifidobacterium and Ruminococcus genera. The Early Matured pattern is enriched in galactose metabolism and exhibits higher production of aromatic amino acids and B-group vitamins at early follow-ups, whereas the Early Plateaued pattern has increased microbial production of branched-chain amino acids. Notably, the Early Plateaued pattern is associated with a threefold elevated risk of T1D, whereas other patterns are not associated with T1D risk. Furthermore, we find that host genetic variants related to antimicrobial and antiviral immune responses modify the association between the Late Matured pattern and T1D risk. These findings highlight the role of early microbial exposures and host genetics in T1D susceptibility. In the prospective, multicentre TEDDY study, distinct patterns of gut microbiome maturation are associated with differential risk of type 1 diabetes, with host genetics modifying the strength of this association.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 10","pages":"2133-2151"},"PeriodicalIF":27.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-026-01614-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

mRNA methylation safeguards pancreatic α-cell identity against cellular plasticity mRNA甲基化保护胰腺α-细胞不受细胞可塑性的影响。

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-09-18 DOI: 10.1038/s42255-026-01594-w

引用次数: 0

m6A mRNA methylation regulates pancreatic α-cell plasticity m6A mRNA甲基化调控胰腺α-细胞可塑性。

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-09-18 DOI: 10.1038/s42255-026-01591-z

Dario F. De Jesus, Natalie K. Brown, Garrett Fogarty, Guilherme Gabriel, Shirong Wang, Shen Wang, Lenee Shrestha, Kristin Kendall, Lily Young, Jiang Hu, Jermaine Austin, Joan Sabadell-Basallote, Sevim Kahraman, Ling Xiao, Rohit N. Kulkarni

{"title":"m6A mRNA methylation regulates pancreatic α-cell plasticity","authors":"Dario F. De Jesus, Natalie K. Brown, Garrett Fogarty, Guilherme Gabriel, Shirong Wang, Shen Wang, Lenee Shrestha, Kristin Kendall, Lily Young, Jiang Hu, Jermaine Austin, Joan Sabadell-Basallote, Sevim Kahraman, Ling Xiao, Rohit N. Kulkarni","doi":"10.1038/s42255-026-01591-z","DOIUrl":"10.1038/s42255-026-01591-z","url":null,"abstract":"Pancreatic α-cells are central regulators of glucose and amino acid homeostasis, yet the mechanisms that preserve α-cell identity and function remain incompletely understood. N6-methyladenosine (m6A) is a widespread mRNA modification that is essential for β-cell biology and pancreatic endocrine differentiation. Here we show that m6A is a key regulator of α-cell function and plasticity. In α-cells, metabolic cues that stimulate glucagon secretion such as L-arginine increase METTL3, METTL14 and m6A levels. Loss of m6A impairs amino acid-stimulated glucagon secretion, disrupts α-cell identity programmes and induces metabolic rewiring. In mice, α-cell-specific Mettl14 deletion reduces α-cell mass, increases β-cell mass and promotes α-to-β-cell conversion, accompanied by the emergence of late β-like states with features of incomplete maturation. Mechanistically, m6A-eCLIP identifies Yy1 as a direct m6A-sensitive target, and elevated YY1 links m6A loss to signalling rewiring and erosion of α-cell identity. These findings identify m6A as a central regulator of α-cell state and reveal an epitranscriptomic mechanism controlling endocrine cell plasticity. m6A methylation acts as an epitranscriptomic regulator of endocrine cell identity in pancreatic islet alpha cells, with loss of m6A leading to impaired alpha cell identity, α- to β-cell conversion and metabolic rewiring of islet endocrine cells.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 9","pages":"1948-1970"},"PeriodicalIF":27.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-026-01591-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of time-restricted eating in early-stage Huntington’s disease: a pilot study 限时饮食对早期亨廷顿舞蹈病的影响：一项初步研究。

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-09-17 DOI: 10.1038/s42255-026-01612-x

Russell G. Wells, Lee E. Neilson, Andrew W. McHill, Nora E. Gray, Joseph F. Quinn, Amie L. Hiller

引用次数: 0

Meal timing as medicine: clinical evidence for intermittent fasting in Huntington’s disease 进餐时间作为药物：间歇性禁食治疗亨廷顿病的临床证据。

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-09-17 DOI: 10.1038/s42255-026-01613-w

引用次数: 0

Cysteine excess triggers a mitochondrial iron-dependent cell death 半胱氨酸过量会引发线粒体铁依赖性细胞死亡。

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-09-15 DOI: 10.1038/s42255-026-01616-7

Toshitaka Nakamura, Ayaka Inoki, Nupur K. Das, Brandon Chen, Artem Khan, Yuyang Liu, Beste Uygur, Frederick S. Yen, Gokhan Unlu, Yatrik M. Shah, Kıvanç Birsoy

{"title":"Cysteine excess triggers a mitochondrial iron-dependent cell death","authors":"Toshitaka Nakamura, Ayaka Inoki, Nupur K. Das, Brandon Chen, Artem Khan, Yuyang Liu, Beste Uygur, Frederick S. Yen, Gokhan Unlu, Yatrik M. Shah, Kıvanç Birsoy","doi":"10.1038/s42255-026-01616-7","DOIUrl":"10.1038/s42255-026-01616-7","url":null,"abstract":"Thiol-containing metabolites are central to cellular redox homeostasis1. Among these, cysteine functions as a proteogenic amino acid, supports redox balance and iron–sulfur cluster biogenesis, and, when depleted, triggers ferroptosis2. Cells nevertheless maintain cysteine at low levels, reflecting its intrinsic toxicity, but the mechanisms by which excess cysteine causes cell death remain unclear3. Here we performed a genome-wide CRISPR screen and identified mitochondrial iron transporters as essential mediators of cysteine toxicity. Limiting mitochondrial iron availability suppresses cysteine-induced cell death and prevents impairment of iron–sulfur cluster proteins and respiration. Mechanistically, cysteine mobilizes iron from ferritin, expands the cytosolic iron pool and drives mitochondrial iron accumulation. Enhancing glutathione reductase activity specifically within mitochondria restores redox balance downstream of iron accumulation and protects cells by maintaining iron–sulfur cluster integrity. Our findings suggest that maintaining low cysteine levels safeguards mitochondrial iron homeostasis, and that excess cysteine triggers a distinct mitochondrial iron-dependent cell death under conditions of thiol imbalance. Using a genome-wide CRISPR screen, the authors demonstrate that excess cysteine drives mitochondrial iron accumulation and iron–sulfur cluster failure, triggering a distinct iron-dependent cell death pathway.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 10","pages":"2102-2116"},"PeriodicalIF":27.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cagrilintide and retatrutide combination therapy enhances weight loss and metabolic outcomes in obese male rats Cagrilintide和reatrutide联合治疗提高肥胖雄性大鼠的体重减轻和代谢结果。

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-09-15 DOI: 10.1038/s42255-026-01603-y

Jonas Petersen, Christoffer Merrild, Stephanie Kjærulff Holm, Nigel Kurgan, Shad Hassan, Cecilie Vad Mathiesen, Stina Börchers, Charlotte Svendsen, Sergio D’Anna, Nicoline R. Andersen, Anders Bue Klein, Andreas M. Fritzen, Atul S. Deshmukh, Tune H. Pers, Christoffer Clemmensen

{"title":"Cagrilintide and retatrutide combination therapy enhances weight loss and metabolic outcomes in obese male rats","authors":"Jonas Petersen, Christoffer Merrild, Stephanie Kjærulff Holm, Nigel Kurgan, Shad Hassan, Cecilie Vad Mathiesen, Stina Börchers, Charlotte Svendsen, Sergio D’Anna, Nicoline R. Andersen, Anders Bue Klein, Andreas M. Fritzen, Atul S. Deshmukh, Tune H. Pers, Christoffer Clemmensen","doi":"10.1038/s42255-026-01603-y","DOIUrl":"10.1038/s42255-026-01603-y","url":null,"abstract":"Peptide multi-receptor agonists have advanced obesity treatment, yet challenges remain in achieving maximal weight loss and metabolic control, especially in patients with obesity and type 2 diabetes. Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats. Daily co-administration produces dose-dependent reductions in body weight and food intake that exceed both equimolar monotherapies and matched-dose comparator combinations incorporating semaglutide or tirzepatide. The combination therapy also improves circulating markers of metabolic health, including cholesterol, triglycerides and insulin levels. Pair-feeding and weight-matching studies reveal that the enhanced weight loss cannot be explained by reduced food intake alone and enable discrimination between weight-loss-dependent and drug-specific molecular responses. Plasma proteomic profiling highlights enrichment of bioenergetic processes with the combination therapy, whereas brain transcriptomic profiling identifies convergent central neuronal programmes linked to energy balance regulation. Collectively, our preclinical findings support five-receptor polypharmacology as a strategy for efficaciously lowering body weight and provide guidance for the design of next-generation unimolecular multi-receptor agonists. Combination therapy with retatrutide and cagrilintide lowers body weight and improves markers of metabolic health in obese, male rats more efficiently than equimolar monotherapies and matched-dose combinations incorporating semaglutide or tirzepatide.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 10","pages":"2069-2083"},"PeriodicalIF":27.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The high price of ‘free’ cysteine “免费”半胱氨酸的高价。

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-09-15 DOI: 10.1038/s42255-026-01620-x

Megan Cheah, Jessalyn M. Ubellacker

引用次数: 0