Nature metabolismPub Date : 2024-09-18DOI: 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":"<p><span>arising from</span> K. Luo et al. <b><i>Nature Metabolism</i></b> https://doi.org/10.1038/s42255-023-00961-1 (2024)</p><p>In the 2024 January issue of <i>Nature Metabolism</i>, Luo et al.<sup>1</sup> 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 (<i>LCT</i>) 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 T2D<sup>2,3</sup> 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.</p>","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}
Nature metabolismPub Date : 2024-09-16DOI: 10.1038/s42255-024-01142-4
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":"Publisher Correction: 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/s42255-024-01142-4","DOIUrl":"https://doi.org/10.1038/s42255-024-01142-4","url":null,"abstract":"","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":18.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291768","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}
Nature metabolismPub Date : 2024-09-11DOI: 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":"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. Wang et al. show how glucose sensing via O-GlcNAcylation drives the assembly of a glycolytic metabolon on the mitochondrial surface to couple metabolic efficiency with neuronal activity.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":18.9,"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}
Nature metabolismPub Date : 2024-09-11DOI: 10.1038/s42255-024-01120-w
{"title":"O-GlcNAc transferase regulates glycolytic metabolon formation on mitochondria to enhance ATP production","authors":"","doi":"10.1038/s42255-024-01120-w","DOIUrl":"10.1038/s42255-024-01120-w","url":null,"abstract":"The metabolic sensor enzyme OGT dynamically O-GlcNAcylates hexokinase 1 (HK1). This modification enhances the localization of HK1 to mitochondria in response to glucose flux and facilitates the formation of a glycolytic metabolon on the mitochondrial outer membrane, leading to increased rates of both glycolytic and mitochondrial ATP production.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":18.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166259","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}
Nature metabolismPub Date : 2024-09-10DOI: 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":"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. Adults with overweight or obesity who exercise regularly for at least 2 years exhibit distinct structural and proteomic characteristics in abdominal subcutaneous adipose tissue that may contribute to better cardiometabolic health outcomes.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":18.9,"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}
Nature metabolismPub Date : 2024-09-10DOI: 10.1038/s42255-024-01102-y
{"title":"Long-term exercise training has positive effects on adipose tissue in overweight or obesity","authors":"","doi":"10.1038/s42255-024-01102-y","DOIUrl":"10.1038/s42255-024-01102-y","url":null,"abstract":"Adults with overweight or obesity who have been exercising regularly for at least a few years have distinct structural and biological characteristics in their abdominal subcutaneous adipose tissue. These changes could underlie improved cardiometabolic health outcomes in this population, when compared with well-matched sedentary adults with overweight or obesity.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":18.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160374","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}
Nature metabolismPub Date : 2024-09-09DOI: 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":"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. Buglakova et al. present 13C-SpaceM, a method that combines stable isotope tracing with imaging mass spectrometry thus enabling spatial analysis of lipid dynamics with near-single-cell resolution in tissues.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":18.9,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42255-024-01118-4.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature metabolismPub Date : 2024-09-06DOI: 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":"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. Sukka et al. delineate a metabolic pathway in macrophages that involves tryptophan uptake and metabolism to drive efferocytosis and subsequent resolution in the context of inflammation.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":18.9,"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}
Nature metabolismPub Date : 2024-09-03DOI: 10.1038/s42255-024-01122-8
Marina Garcia-Macia, Fei Yin
{"title":"Career pathways, part 15","authors":"Marina Garcia-Macia, Fei Yin","doi":"10.1038/s42255-024-01122-8","DOIUrl":"10.1038/s42255-024-01122-8","url":null,"abstract":"In this new instalment of our Career Pathways series, Marina García-Macia and Fei Yin highlight the impact and joys of building a team and share with us key milestones that have shaped their careers so far, including the importance of making the most of every situation, finding the right mentors, and pursuing the questions that they are passionate about.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":18.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123490","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}
Nature metabolismPub Date : 2024-09-02DOI: 10.1038/s42255-024-01124-6
Alessandro Bitto
{"title":"Mitochondrial transplants to treat mitochondrial dysfunction","authors":"Alessandro Bitto","doi":"10.1038/s42255-024-01124-6","DOIUrl":"10.1038/s42255-024-01124-6","url":null,"abstract":"A new approach to treating mitochondrial disorders is based on the transplantation of healthy mitochondria, and improves symptoms and survival in a mouse model of Leigh syndrome — a paediatric mitochondrial disease that is characterized by failure to thrive, lactic acidosis, and progressive degeneration.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":18.9,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118121","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}