Nature metabolism最新文献

Sweet signals for myelin: glucose sensing redirected to regeneration. 髓磷脂的甜蜜信号：葡萄糖传感重定向到再生。

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-10-22 DOI: 10.1038/s42255-025-01392-w

Andrew R Tee

引用次数: 0

Oligodendrocyte precursor cell-specific blocking of low-glucose-induced activation of AMPK ensures myelination and remyelination. 少突胶质前体细胞特异性阻断低糖诱导的AMPK激活，确保髓鞘形成和再髓鞘形成。

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-10-22 DOI: 10.1038/s42255-025-01386-8

Yuxia Sun,Wei-Wei Zhang,Lu Men,Jianfeng Wu,Luming Yao,Xi Huang,Yaying Wu,Cixiong Zhang,Ying Chen,David Carling,Chen-Song Zhang,Sheng-Cai Lin

引用次数: 0

Microbial metabolite indole-3-propionic acid drives mitochondrial respiration in CD4+ T cells to confer protection against intestinal inflammation. 微生物代谢物吲哚-3-丙酸驱动CD4+ T细胞的线粒体呼吸，以保护机体免受肠道炎症。

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-10-21 DOI: 10.1038/s42255-025-01396-6

Qing Li,Rodrigo de Oliveira Formiga,Virginie Puchois,Laura Creusot,Ahmad Haidar Ahmad,Salomé Amouyal,Márcio Augusto Campos-Ribeiro,Yining Zhao,Danielle M M Harris,Frederic Lasserre,Sandrine Ellero-Simatos,Hervé Guillou,Zhan Huang,Loic Brot,Yuhang Hu,Loic Chollet,Camille Danne,Cyril Scandola,Tatiana Ledent,Guillaume Chevreux,Rafael J Argüello,Marcelo De Carvalho Bittencourt,Jessica Bettinger,Maud D'Aveni-Piney,David Moulin,Stefan Schreiber,Konrad Aden,Nathalie Rolhion,Marie-Laure Michel,Timothy Wai,Harry Sokol

{"title":"Microbial metabolite indole-3-propionic acid drives mitochondrial respiration in CD4+ T cells to confer protection against intestinal inflammation.","authors":"Qing Li,Rodrigo de Oliveira Formiga,Virginie Puchois,Laura Creusot,Ahmad Haidar Ahmad,Salomé Amouyal,Márcio Augusto Campos-Ribeiro,Yining Zhao,Danielle M M Harris,Frederic Lasserre,Sandrine Ellero-Simatos,Hervé Guillou,Zhan Huang,Loic Brot,Yuhang Hu,Loic Chollet,Camille Danne,Cyril Scandola,Tatiana Ledent,Guillaume Chevreux,Rafael J Argüello,Marcelo De Carvalho Bittencourt,Jessica Bettinger,Maud D'Aveni-Piney,David Moulin,Stefan Schreiber,Konrad Aden,Nathalie Rolhion,Marie-Laure Michel,Timothy Wai,Harry Sokol","doi":"10.1038/s42255-025-01396-6","DOIUrl":"https://doi.org/10.1038/s42255-025-01396-6","url":null,"abstract":"The gut microbiota and its metabolites critically regulate immune cell phenotype, function and energy metabolism. We screened a collection of gut microbiota-related metabolites to identify modulators of mitochondrial metabolism in T cells. Here we show that indole-3-propionic acid (IPA) stimulates mitochondrial respiration of CD4+ T cells by increasing fatty acid oxidation (FAO) and amino acid oxidation (AAO), while inhibiting glycolytic capacity. IPA also impacts CD4+ T cell behaviour by inhibiting their differentiation to type 1 and type 17 helper T cell phenotypes. Mechanistically, the metabolic and immune effects of IPA are mediated by peroxisome proliferator-activated receptor-β/δ. The administration of IPA rescues mitochondria respiration in mice with gut bacteria depletion or colitis by enhancing FAO and AAO in colonic CD4+ T cells. Adoptive transfer experiments show that IPA acts on CD4+ T cells to exert its protective effect against inflammation. Collectively, our study reveals that the anti-inflammatory effects of IPA are mediated by metabolic reprogramming of CD4+ T cells toward the enhancement of mitochondrial respiration.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"32 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338529","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

IPA brews metabolic balance in gut immunity. IPA促进肠道免疫代谢平衡。

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-10-21 DOI: 10.1038/s42255-025-01401-y

Jacy Scott,Chaoran Li

引用次数: 0

A lactate-acetate interaction between macrophages and cancer cells drives metastasis. 巨噬细胞和癌细胞之间的乳酸-乙酸相互作用驱动转移。

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-10-20 DOI: 10.1038/s42255-025-01398-4

引用次数: 0

Tumour-associated macrophages serve as an acetate reservoir to drive hepatocellular carcinoma metastasis. 肿瘤相关巨噬细胞作为醋酸盐储存库驱动肝细胞癌转移。

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-10-20 DOI: 10.1038/s42255-025-01393-9

Li Shen,Shenghao Wang,Chao Gao,Qin Li,Shuya Feng,Weiyan Sun,Xu Liu,Yiyi Ba,Yihui Chu,Yu Zhou,Junjie Pan,Hao Xu,Xu Zhang,Wenwei Zhu,Lunxiu Qin,Ming Lu

{"title":"Tumour-associated macrophages serve as an acetate reservoir to drive hepatocellular carcinoma metastasis.","authors":"Li Shen,Shenghao Wang,Chao Gao,Qin Li,Shuya Feng,Weiyan Sun,Xu Liu,Yiyi Ba,Yihui Chu,Yu Zhou,Junjie Pan,Hao Xu,Xu Zhang,Wenwei Zhu,Lunxiu Qin,Ming Lu","doi":"10.1038/s42255-025-01393-9","DOIUrl":"https://doi.org/10.1038/s42255-025-01393-9","url":null,"abstract":"Increased acetyl-coenzyme A (acetyl-CoA) generation facilitates cancer metastasis and represents a critical metabolic characteristic of metastatic cancers. To maintain high acetyl-CoA levels, cancer cells often enhance the uptake of acetate for acetyl-CoA biosynthesis. However, the microenvironmental source of acetate remains largely unknown. Here we demonstrate that acetate is secreted by tumour-associated macrophages (TAMs) and taken up by hepatocellular carcinoma (HCC) cells to support acetate accumulation. Mechanistically, HCC cell-derived lactate activates the lipid peroxidation-aldehyde dehydrogenase 2 (ALDH2) pathway in TAMs, which promotes the TAMs' acetate production and secretion. Inhibition of ALDH2 or of lipid peroxidation in TAMs abrogates acetate-induced migration of HCC cells in vitro. In an orthotopic HCC model involving male mice, genetic ablation of ALDH2 in TAMs reduces HCC cell acetate levels and HCC lung metastases. Collectively, our findings reveal a metabolic interaction between HCC cells and TAMs-involving lactate, lipid peroxidation and acetate-and position TAMs as an acetate reservoir that drives HCC metastasis.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"134 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331578","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

Human genetics of steatotic liver disease: insights into insulin resistance and lipid metabolism. 脂肪变性肝病的人类遗传学：胰岛素抵抗和脂质代谢。

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-10-17 DOI: 10.1038/s42255-025-01394-8

Rosellina M Mancina,Luca Valenti,Stefano Romeo

{"title":"Human genetics of steatotic liver disease: insights into insulin resistance and lipid metabolism.","authors":"Rosellina M Mancina,Luca Valenti,Stefano Romeo","doi":"10.1038/s42255-025-01394-8","DOIUrl":"https://doi.org/10.1038/s42255-025-01394-8","url":null,"abstract":"Metabolic-dysfunction-associated steatotic liver disease (MASLD, previously known as non-alcoholic fatty liver disease or NAFLD) is a prevalent and heterogeneous condition affecting nearly 30% of the global population. MASLD is defined as excessive hepatic lipid accumulation with at least one feature of insulin resistance, with potential progression to metabolic dysfunction-associated steatohepatitis, cirrhosis and hepatocellular carcinoma. The disease often coexists with insulin resistance and cardiovascular and chronic kidney diseases. Human genetics has shed light on MASLD predisposition and its causal association with type 2 diabetes and insulin resistance, enabling the field to progress towards precision-medicine therapeutics. Convergent selection of somatic mutations in genes involved in glucose and lipid metabolism in cirrhotic livers suggests adaptive responses to gluco-lipotoxicity that influence end-stage liver disease. Recently, two distinct types of MASLD, with specific clinical trajectories, were identified on the basis of partitioned polygenic risk scores. Future studies are needed to integrate this knowledge, enabling earlier detection, risk stratification and targeted therapies.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"1 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311701","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

Interaction of sortilin with apolipoprotein E3 enables neurons to use long-chain fatty acids as alternative metabolic fuel. sortilin与载脂蛋白E3的相互作用使神经元使用长链脂肪酸作为替代代谢燃料。

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-10-16 DOI: 10.1038/s42255-025-01389-5

Anna K Greda, Jemila P Gomes, Vanessa Schmidt-Krueger, Ewa Zurawska-Plaksej, Raphaela Fritsche-Guenther, Ina-Maria Rudolph, Narasimha S Telugu, Cagla Cömert, Jennifer Kirwan, Séverine Kunz, Michael Rothe, Mogens Johannsen, Sebastian Diecke, Peter Bross, Thomas E Willnow

{"title":"Interaction of sortilin with apolipoprotein E3 enables neurons to use long-chain fatty acids as alternative metabolic fuel.","authors":"Anna K Greda, Jemila P Gomes, Vanessa Schmidt-Krueger, Ewa Zurawska-Plaksej, Raphaela Fritsche-Guenther, Ina-Maria Rudolph, Narasimha S Telugu, Cagla Cömert, Jennifer Kirwan, Séverine Kunz, Michael Rothe, Mogens Johannsen, Sebastian Diecke, Peter Bross, Thomas E Willnow","doi":"10.1038/s42255-025-01389-5","DOIUrl":"https://doi.org/10.1038/s42255-025-01389-5","url":null,"abstract":"<p><p>Sortilin (SORT1) is a lipoprotein receptor that shows genome-wide association with hypercholesterolaemia, explained by its ability to control hepatic output of lipoproteins. Although SORT1 also shows genome-wide association with Alzheimer disease and frontotemporal lobe dementia, the most prevalent forms of age-related dementias, sortilin's contribution to human brain lipid metabolism and health remains unclear. Here we show that sortilin mediates neuronal uptake of polyunsaturated fatty acids carried by apolipoprotein E (apoE). Using humanized mouse strains and induced pluripotent stem cell-based cell models of brain lipid homeostasis, we demonstrate that internalized lipids are converted into ligands for peroxisome proliferator-activated receptor alpha inducing transcription profiles that enable neurons to use long-chain fatty acids as metabolic fuel when glucose is limited. This pathway works with apoE3 but cannot operate with the Alzheimer disease risk factor apoE4, which disrupts sortilin's endocytic activity. Our data indicate a role for the lipoprotein receptor sortilin in metabolic fuel choice in neurons, which may be crucial when glucose supply is limited, such as in the ageing brain.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":" ","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308602","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

EMito-Metrix enables automated evaluation of mitochondrial morphology across species. EMito-Metrix能够自动评估跨物种的线粒体形态。

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-10-15 DOI: 10.1038/s42255-025-01400-z

Eléna Morin,Emmanuel Doumard,Lisa M Hartnell,Beñat Salegi Ansa,Jean-Philippe Leduc-Gaudet,Aurélie Quillien,Jean Nakhle,Séverine Ethuin,Dominique Goudounèche,Bruno Payré,Vanessa Soldan,Stéphanie Balor,Anna Mattout,Jacques Rouquette,Laurence Dubois,Coralie Sengenès,Valérie Planat,Louis Casteilla,Armelle Yart,Cédric Dray,Julien Aligon,Luigi Ferrucci,Élise Duchesne,Sabah N A Hussain,Gilles Gouspillou,Laura Formentini,Arnaud Mourier,Olivier R Baris,Philippe Valet,Harold Parpex,Paul Monsarrat,Mathieu Vigneau,Jean-Philippe Pradère

引用次数: 0

Mitochondrial and psychosocial stress-related regulation of FGF21 in humans. 人类FGF21的线粒体和社会心理应激相关调控。

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-10-14 DOI: 10.1038/s42255-025-01388-6

Mangesh Kurade,Natalia Bobba-Alves,Catherine Kelly,Alexander Behnke,Quinn Conklin,Robert-Paul Juster,Michio Hirano,Caroline Trumpff,Martin Picard

引用次数: 0