Nature metabolism最新文献

Reply to: Milk intake, lactase non-persistence and type 2 diabetes risk in Chinese adults 答复中国成年人的牛奶摄入量、乳糖不耐受性与 2 型糖尿病风险

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-09-18 DOI: 10.1038/s42255-024-01129-1

Kai Luo, Yanbo Zhang, Robert C. Kaplan, Qibin Qi

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Milk intake, lactase non-persistence and type 2 diabetes risk in Chinese adults 中国成年人的牛奶摄入量、乳糖不耐受性与 2 型糖尿病风险

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-09-18 DOI: 10.1038/s42255-024-01128-2

Maria G. Kakkoura, Robin G. Walters, Robert Clarke, Zhengming Chen, Huaidong Du

{"title":"Milk intake, lactase non-persistence and type 2 diabetes risk in Chinese adults","authors":"Maria G. Kakkoura, Robin G. Walters, Robert Clarke, Zhengming Chen, Huaidong Du","doi":"10.1038/s42255-024-01128-2","DOIUrl":"https://doi.org/10.1038/s42255-024-01128-2","url":null,"abstract":"arising from K. Luo et al. Nature Metabolism https://doi.org/10.1038/s42255-023-00961-1 (2024)In the 2024 January issue of Nature Metabolism, Luo et al.1 reported an inverse association between milk intake and risk of type 2 diabetes (T2D) among individuals who were lactase non-persistent (LNP), as determined by the lactase (LCT) rs4988235 homozygous GG genotype. The authors also reported inverse cross-sectional associations of milk intake with several T2D-related metabolic traits, including body mass index (BMI) and waist circumference (WC) in LNP individuals. However, in their analyses, no adjustments for BMI/WC were done in assessing the association between milk intake and T2D risk, which may lead to biased results. Given the established causal relevance of adiposity for incident T2D2,3 and the observed inverse associations of milk intake with adiposity in the study population, it is therefore important to establish whether the associations of milk consumption, milk-associated gut bacteria and milk-associated metabolites with T2D risk are confounded, or mediated, by BMI/WC in the paper by Luo et al.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":20.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236226","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}

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Organization of a functional glycolytic metabolon on mitochondria for metabolic efficiency 在线粒体上组织功能性糖酵解代谢子以提高代谢效率

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-09-11 DOI: 10.1038/s42255-024-01121-9

Haoming Wang, John W. Vant, Andrew Zhang, Richard G. Sanchez, Youjun Wu, Mary L. Micou, Vincent Luczak, Zachary Whiddon, Natasha M. Carlson, Seungyoon B. Yu, Mirna Jabbo, Seokjun Yoon, Ahmed A. Abushawish, Majid Ghassemian, Takeya Masubuchi, Quan Gan, Shigeki Watanabe, Eric R. Griffis, Marc Hammarlund, Abhishek Singharoy, Gulcin Pekkurnaz

{"title":"Organization of a functional glycolytic metabolon on mitochondria for metabolic efficiency","authors":"Haoming Wang, John W. Vant, Andrew Zhang, Richard G. Sanchez, Youjun Wu, Mary L. Micou, Vincent Luczak, Zachary Whiddon, Natasha M. Carlson, Seungyoon B. Yu, Mirna Jabbo, Seokjun Yoon, Ahmed A. Abushawish, Majid Ghassemian, Takeya Masubuchi, Quan Gan, Shigeki Watanabe, Eric R. Griffis, Marc Hammarlund, Abhishek Singharoy, Gulcin Pekkurnaz","doi":"10.1038/s42255-024-01121-9","DOIUrl":"https://doi.org/10.1038/s42255-024-01121-9","url":null,"abstract":"Glucose, the primary cellular energy source, is metabolized through glycolysis initiated by the rate-limiting enzyme hexokinase (HK). In energy-demanding tissues like the brain, HK1 is the dominant isoform, primarily localized on mitochondria, and is crucial for efficient glycolysis–oxidative phosphorylation coupling and optimal energy generation. This study unveils a unique mechanism regulating HK1 activity, glycolysis and the dynamics of mitochondrial coupling, mediated by the metabolic sensor enzyme O-GlcNAc transferase (OGT). OGT catalyses reversible O-GlcNAcylation, a post-translational modification influenced by glucose flux. Elevated OGT activity induces dynamic O-GlcNAcylation of the regulatory domain of HK1, subsequently promoting the assembly of the glycolytic metabolon on the outer mitochondrial membrane. This modification enhances the mitochondrial association with HK1, orchestrating glycolytic and mitochondrial ATP production. Mutation in HK1’s O-GlcNAcylation site reduces ATP generation in multiple cell types, specifically affecting metabolic efficiency in neurons. This study reveals a previously unappreciated pathway that links neuronal metabolism and mitochondrial function through OGT and the formation of the glycolytic metabolon, providing potential strategies for tackling metabolic and neurological disorders.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":20.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166288","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}

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O-GlcNAc transferase regulates glycolytic metabolon formation on mitochondria to enhance ATP production O-GlcNAc 转移酶调节线粒体上糖酵解代谢物的形成，以提高 ATP 的产生

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-09-11 DOI: 10.1038/s42255-024-01120-w

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Years of endurance exercise training remodel abdominal subcutaneous adipose tissue in adults with overweight or obesity 多年耐力运动训练重塑超重或肥胖成人的腹部皮下脂肪组织

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-09-10 DOI: 10.1038/s42255-024-01103-x

Cheehoon Ahn, Tao Zhang, Gayoung Yang, Thomas Rode, Pallavi Varshney, Sophia J. Ghayur, Olivia K. Chugh, Hui Jiang, Jeffrey F. Horowitz

{"title":"Years of endurance exercise training remodel abdominal subcutaneous adipose tissue in adults with overweight or obesity","authors":"Cheehoon Ahn, Tao Zhang, Gayoung Yang, Thomas Rode, Pallavi Varshney, Sophia J. Ghayur, Olivia K. Chugh, Hui Jiang, Jeffrey F. Horowitz","doi":"10.1038/s42255-024-01103-x","DOIUrl":"https://doi.org/10.1038/s42255-024-01103-x","url":null,"abstract":"Abnormalities in the structure and metabolic function of abdominal subcutaneous adipose tissue (aSAT) underlie many obesity-related health complications. Endurance exercise improves cardiometabolic health in adults with overweight or obesity, but the effects of endurance training on aSAT are unclear. We included male and female participants who were regular exercisers with overweight or obesity who exercised for >2 years, and cross-sectionally compared them with well-matched non-exercisers with overweight or obesity. Here we show aSAT from exercisers has a higher capillary density, lower Col6a abundance and fewer macrophages compared with non-exercisers. This is accompanied by a greater abundance of angiogenic, ribosomal, mitochondrial and lipogenic proteins. The abundance of phosphoproteins involved in protein translation, lipogenesis and direct regulation of transcripts is also greater in aSAT collected from exercisers. Exploratory ex vivo experiments demonstrate greater angiogenic capacity and higher lipid-storage capacity in samples cultured from aSAT collected from exercisers versus non-exercisers. Regular exercise may play a role in remodelling aSAT structure and proteomic profile in ways that may contribute to preserved cardiometabolic health.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":20.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160375","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}

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Long-term exercise training has positive effects on adipose tissue in overweight or obesity 长期运动训练对超重或肥胖症患者的脂肪组织有积极影响

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-09-10 DOI: 10.1038/s42255-024-01102-y

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Spatial single-cell isotope tracing reveals heterogeneity of de novo fatty acid synthesis in cancer 空间单细胞同位素追踪揭示癌症中脂肪酸合成的异质性

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-09-09 DOI: 10.1038/s42255-024-01118-4

Elena Buglakova, Måns Ekelöf, Michaela Schwaiger-Haber, Lisa Schlicker, Martijn R. Molenaar, Mohammed Shahraz, Lachlan Stuart, Andreas Eisenbarth, Volker Hilsenstein, Gary J. Patti, Almut Schulze, Marteinn T. Snaebjornsson, Theodore Alexandrov

{"title":"Spatial single-cell isotope tracing reveals heterogeneity of de novo fatty acid synthesis in cancer","authors":"Elena Buglakova, Måns Ekelöf, Michaela Schwaiger-Haber, Lisa Schlicker, Martijn R. Molenaar, Mohammed Shahraz, Lachlan Stuart, Andreas Eisenbarth, Volker Hilsenstein, Gary J. Patti, Almut Schulze, Marteinn T. Snaebjornsson, Theodore Alexandrov","doi":"10.1038/s42255-024-01118-4","DOIUrl":"https://doi.org/10.1038/s42255-024-01118-4","url":null,"abstract":"While heterogeneity is a key feature of cancer, understanding metabolic heterogeneity at the single-cell level remains a challenge. Here we present 13C-SpaceM, a method for spatial single-cell isotope tracing that extends the previously published SpaceM method with detection of 13C6-glucose-derived carbons in esterified fatty acids. We validated 13C-SpaceM on spatially heterogeneous models using liver cancer cells subjected to either normoxia-hypoxia or ATP citrate lyase depletion. This revealed substantial single-cell heterogeneity in labelling of the lipogenic acetyl-CoA pool and in relative fatty acid uptake versus synthesis hidden in bulk analyses. Analysing tumour-bearing brain tissue from mice fed a 13C6-glucose-containing diet, we found higher glucose-dependent synthesis of saturated fatty acids and increased elongation of essential fatty acids in tumours compared with healthy brains. Furthermore, our analysis uncovered spatial heterogeneity in lipogenic acetyl-CoA pool labelling in tumours. Our method enhances spatial probing of metabolic activities in single cells and tissues, providing insights into fatty acid metabolism in homoeostasis and disease.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":20.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158969","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}

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Efferocytosis drives a tryptophan metabolism pathway in macrophages to promote tissue resolution 吞噬作用驱动巨噬细胞中的色氨酸代谢途径，促进组织修复

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-09-06 DOI: 10.1038/s42255-024-01115-7

Santosh R. Sukka, Patrick B. Ampomah, Lancia N. F. Darville, David Ngai, Xiaobo Wang, George Kuriakose, Yuling Xiao, Jinjun Shi, John M. Koomen, Robert H. McCusker, Ira Tabas

{"title":"Efferocytosis drives a tryptophan metabolism pathway in macrophages to promote tissue resolution","authors":"Santosh R. Sukka, Patrick B. Ampomah, Lancia N. F. Darville, David Ngai, Xiaobo Wang, George Kuriakose, Yuling Xiao, Jinjun Shi, John M. Koomen, Robert H. McCusker, Ira Tabas","doi":"10.1038/s42255-024-01115-7","DOIUrl":"https://doi.org/10.1038/s42255-024-01115-7","url":null,"abstract":"Macrophage efferocytosis prevents apoptotic cell (AC) accumulation and triggers inflammation-resolution pathways. The mechanisms linking efferocytosis to resolution often involve changes in macrophage metabolism, but many gaps remain in our understanding of these processes. We now report that efferocytosis triggers an indoleamine 2,3-dioxygenase-1 (IDO1)-dependent tryptophan (Trp) metabolism pathway that promotes several key resolution processes, including the induction of pro-resolving proteins, such interleukin-10, and further enhancement of efferocytosis. The process begins with upregulation of Trp transport and metabolism, and it involves subsequent activation of the aryl hydrocarbon receptor (AhR) by the Trp metabolite kynurenine (Kyn). Through these mechanisms, macrophage IDO1 and AhR contribute to a proper resolution response in several different mouse models of efferocytosis-dependent tissue repair, notably during atherosclerosis regression induced by plasma low-density lipoprotein (LDL) lowering. These findings reveal an integrated metabolism programme in macrophages that links efferocytosis to resolution, with possible therapeutic implications for non-resolving chronic inflammatory diseases, notably atherosclerosis.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":20.8,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142411","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}

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Career pathways, part 15 职业途径，第 15 部分

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-09-03 DOI: 10.1038/s42255-024-01122-8

Marina Garcia-Macia, Fei Yin

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Mitochondrial transplants to treat mitochondrial dysfunction 线粒体移植治疗线粒体功能障碍

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-09-02 DOI: 10.1038/s42255-024-01124-6

Alessandro Bitto

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