Nature metabolismPub Date : 2024-07-19DOI: 10.1038/s42255-024-01086-9
Naisi Zhao, Guojun Wu, Liping Zhao
{"title":"H2S as a metabolic saboteur","authors":"Naisi Zhao, Guojun Wu, Liping Zhao","doi":"10.1038/s42255-024-01086-9","DOIUrl":"10.1038/s42255-024-01086-9","url":null,"abstract":"In this issue of Nature Metabolism, Qi and colleagues show that the gut microbiota members Desulfovibrio spp. produce hydrogen sulfide, which disrupts host metabolism by suppressing GLP-1 production in mice. The study unveils a microbial mechanism that affects metabolic health.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 8","pages":"1431-1432"},"PeriodicalIF":18.9,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727549","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 : 2024-07-15DOI: 10.1038/s42255-024-01084-x
John A. Haley, David A. Guertin
{"title":"Adipose glutaminolysis resurfaces in metabolic disease","authors":"John A. Haley, David A. Guertin","doi":"10.1038/s42255-024-01084-x","DOIUrl":"10.1038/s42255-024-01084-x","url":null,"abstract":"Analysis of glutamine metabolism in white adipose tissue (WAT) uncovers a novel role in metabolic disease that could be leveraged in therapies to combat disease.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 7","pages":"1200-1201"},"PeriodicalIF":18.9,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618208","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 : 2024-07-15DOI: 10.1038/s42255-024-01083-y
Simon Lecoutre, Salwan Maqdasy, David Rizo-Roca, Gianluca Renzi, Ivan Vlassakev, Lynn M. Alaeddine, Romane Higos, Jutta Jalkanen, Jiawei Zhong, Danae S. Zareifi, Scott Frendo-Cumbo, Lucas Massier, Ondrej Hodek, Marta Juvany, Thomas Moritz, Thais de Castro Barbosa, Muhmmad Omar-Hmeadi, Marta López-Yus, Fatiha Merabtene, Jimon Boniface Abatan, Geneviève Marcelin, Elie-Julien El Hachem, Christine Rouault, Martin O. Bergo, Paul Petrus, Juleen R. Zierath, Karine Clément, Anna Krook, Niklas Mejhert, Mikael Rydén
{"title":"Reduced adipocyte glutaminase activity promotes energy expenditure and metabolic health","authors":"Simon Lecoutre, Salwan Maqdasy, David Rizo-Roca, Gianluca Renzi, Ivan Vlassakev, Lynn M. Alaeddine, Romane Higos, Jutta Jalkanen, Jiawei Zhong, Danae S. Zareifi, Scott Frendo-Cumbo, Lucas Massier, Ondrej Hodek, Marta Juvany, Thomas Moritz, Thais de Castro Barbosa, Muhmmad Omar-Hmeadi, Marta López-Yus, Fatiha Merabtene, Jimon Boniface Abatan, Geneviève Marcelin, Elie-Julien El Hachem, Christine Rouault, Martin O. Bergo, Paul Petrus, Juleen R. Zierath, Karine Clément, Anna Krook, Niklas Mejhert, Mikael Rydén","doi":"10.1038/s42255-024-01083-y","DOIUrl":"10.1038/s42255-024-01083-y","url":null,"abstract":"Glutamine and glutamate are interconverted by several enzymes and alterations in this metabolic cycle are linked to cardiometabolic traits. Herein, we show that obesity-associated insulin resistance is characterized by decreased plasma and white adipose tissue glutamine-to-glutamate ratios. We couple these stoichiometric changes to perturbed fat cell glutaminase and glutamine synthase messenger RNA and protein abundance, which together promote glutaminolysis. In human white adipocytes, reductions in glutaminase activity promote aerobic glycolysis and mitochondrial oxidative capacity via increases in hypoxia-inducible factor 1α abundance, lactate levels and p38 mitogen-activated protein kinase signalling. Systemic glutaminase inhibition in male and female mice, or genetically in adipocytes of male mice, triggers the activation of thermogenic gene programs in inguinal adipocytes. Consequently, the knockout mice display higher energy expenditure and improved glucose tolerance compared to control littermates, even under high-fat diet conditions. Altogether, our findings highlight white adipocyte glutamine turnover as an important determinant of energy expenditure and metabolic health. Lecoutre, Maqdasy and Rizo-Roca show that whole-body pharmacological inhibition or adipocyte-specific deletion of glutaminase in mice activates thermogenesis in inguinal adipocytes and promotes metabolic health. They also link decreased plasma and adipose tissue glutamine-to-glutamate ratios to insulin resistance in humans with obesity.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 7","pages":"1329-1346"},"PeriodicalIF":18.9,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42255-024-01083-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618207","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 : 2024-07-12DOI: 10.1038/s42255-024-01079-8
Ophélia Le Thuc, Cristina García-Cáceres
{"title":"Obesity-induced inflammation: connecting the periphery to the brain","authors":"Ophélia Le Thuc, Cristina García-Cáceres","doi":"10.1038/s42255-024-01079-8","DOIUrl":"10.1038/s42255-024-01079-8","url":null,"abstract":"Obesity is often associated with a chronic, low-grade inflammatory state affecting the entire body. This sustained inflammatory state disrupts the coordinated communication between the periphery and the brain, which has a crucial role in maintaining homeostasis through humoural, nutrient-mediated, immune and nervous signalling pathways. The inflammatory changes induced by obesity specifically affect communication interfaces, including the blood–brain barrier, glymphatic system and meninges. Consequently, brain areas near the third ventricle, including the hypothalamus and other cognition-relevant regions, become susceptible to impairments, resulting in energy homeostasis dysregulation and an elevated risk of cognitive impairments such as Alzheimer’s disease and dementia. This Review explores the intricate communication between the brain and the periphery, highlighting the effect of obesity-induced inflammation on brain function. Le Thuc and García-Cáceres discuss the effect of obesity-induced systemic inflammation on the brain, including hypothalamic circuits for whole-body energy homeostasis as well as cognitive function.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 7","pages":"1237-1252"},"PeriodicalIF":18.9,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597346","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 : 2024-07-05DOI: 10.1038/s42255-024-01094-9
Theresa V. Rohm, Felipe Castellani Gomes Dos Reis, Roi Isaac, Cairo Murphy, Karina Cunha e Rocha, Gautam Bandyopadhyay, Hong Gao, Avraham M. Libster, Rizaldy C. Zapata, Yun Sok Lee, Wei Ying, Charlene Miciano, Allen Wang, Jerrold M. Olefsky
{"title":"Author Correction: Adipose tissue macrophages secrete small extracellular vesicles that mediate rosiglitazone-induced insulin sensitization","authors":"Theresa V. Rohm, Felipe Castellani Gomes Dos Reis, Roi Isaac, Cairo Murphy, Karina Cunha e Rocha, Gautam Bandyopadhyay, Hong Gao, Avraham M. Libster, Rizaldy C. Zapata, Yun Sok Lee, Wei Ying, Charlene Miciano, Allen Wang, Jerrold M. Olefsky","doi":"10.1038/s42255-024-01094-9","DOIUrl":"10.1038/s42255-024-01094-9","url":null,"abstract":"","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 8","pages":"1646-1646"},"PeriodicalIF":18.9,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42255-024-01094-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538243","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 : 2024-07-03DOI: 10.1038/s42255-024-01074-z
Cecilia Noecker, Peter J. Turnbaugh
{"title":"Emerging tools and best practices for studying gut microbial community metabolism","authors":"Cecilia Noecker, Peter J. Turnbaugh","doi":"10.1038/s42255-024-01074-z","DOIUrl":"10.1038/s42255-024-01074-z","url":null,"abstract":"The human gut microbiome vastly extends the set of metabolic reactions catalysed by our own cells, with far-reaching consequences for host health and disease. However, our knowledge of gut microbial metabolism relies on a handful of model organisms, limiting our ability to interpret and predict the metabolism of complex microbial communities. In this Perspective, we discuss emerging tools for analysing and modelling the metabolism of gut microorganisms and for linking microorganisms, pathways and metabolites at the ecosystem level, highlighting promising best practices for researchers. Continued progress in this area will also require infrastructure development to facilitate cross-disciplinary synthesis of scientific findings. Collectively, these efforts can enable a broader and deeper understanding of the workings of the gut ecosystem and open new possibilities for microbiome manipulation and therapy. In this Perspective, Noecker and Turnbaugh provide a detailed guide for studying microbial community metabolism and discuss the best practices in the field.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 7","pages":"1225-1236"},"PeriodicalIF":18.9,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141495904","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 : 2024-07-03DOI: 10.1038/s42255-024-01078-9
Qingzhang Zhu, Shiuhwei Chen, Jan-Bernd Funcke, Leon G. Straub, Qian Lin, Shangang Zhao, Chanmin Joung, Zhuzhen Zhang, Dae-Seok Kim, Na Li, Christy M. Gliniak, Charlotte Lee, Alberto Cebrian-Serrano, Line Pedersen, Nils Halberg, Ruth Gordillo, Christine M. Kusminski, Philipp E. Scherer
{"title":"PAQR4 regulates adipocyte function and systemic metabolic health by mediating ceramide levels","authors":"Qingzhang Zhu, Shiuhwei Chen, Jan-Bernd Funcke, Leon G. Straub, Qian Lin, Shangang Zhao, Chanmin Joung, Zhuzhen Zhang, Dae-Seok Kim, Na Li, Christy M. Gliniak, Charlotte Lee, Alberto Cebrian-Serrano, Line Pedersen, Nils Halberg, Ruth Gordillo, Christine M. Kusminski, Philipp E. Scherer","doi":"10.1038/s42255-024-01078-9","DOIUrl":"10.1038/s42255-024-01078-9","url":null,"abstract":"PAQR4 is an orphan receptor in the PAQR family with an unknown function in metabolism. Here, we identify a critical role of PAQR4 in maintaining adipose tissue function and whole-body metabolic health. We demonstrate that expression of Paqr4 specifically in adipocytes, in an inducible and reversible fashion, leads to partial lipodystrophy, hyperglycaemia and hyperinsulinaemia, which is ameliorated by wild-type adipose tissue transplants or leptin treatment. By contrast, deletion of Paqr4 in adipocytes improves healthy adipose remodelling and glucose homoeostasis in diet-induced obesity. Mechanistically, PAQR4 regulates ceramide levels by mediating the stability of ceramide synthases (CERS2 and CERS5) and, thus, their activities. Overactivation of the PQAR4–CERS axis causes ceramide accumulation and impairs adipose tissue function through suppressing adipogenesis and triggering adipocyte de-differentiation. Blocking de novo ceramide biosynthesis rescues PAQR4-induced metabolic defects. Collectively, our findings suggest a critical function of PAQR4 in regulating cellular ceramide homoeostasis and targeting PAQR4 offers an approach for the treatment of metabolic disorders. PAQR4 regulates cellular ceramide synthesis and accumulation to mediate adipose tissue function, glucose homoeostasis and, thus, systemic metabolic health.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 7","pages":"1347-1366"},"PeriodicalIF":18.9,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496027","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 : 2024-07-02DOI: 10.1038/s42255-024-01091-y
Anna L. Gloyn, Mark Ibberson, Piero Marchetti, Alvin C. Powers, Patrik Rorsman, Maike Sander, Michele Solimena
{"title":"Author Correction: Every islet matters: improving the impact of human islet research","authors":"Anna L. Gloyn, Mark Ibberson, Piero Marchetti, Alvin C. Powers, Patrik Rorsman, Maike Sander, Michele Solimena","doi":"10.1038/s42255-024-01091-y","DOIUrl":"10.1038/s42255-024-01091-y","url":null,"abstract":"","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 7","pages":"1415-1415"},"PeriodicalIF":18.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42255-024-01091-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492720","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 : 2024-07-02DOI: 10.1038/s42255-024-01067-y
Cătălina Cuparencu, Tuğçe Bulmuş-Tüccar, Jan Stanstrup, Giorgia La Barbera, Henrik M. Roager, Lars O. Dragsted
{"title":"Towards nutrition with precision: unlocking biomarkers as dietary assessment tools","authors":"Cătălina Cuparencu, Tuğçe Bulmuş-Tüccar, Jan Stanstrup, Giorgia La Barbera, Henrik M. Roager, Lars O. Dragsted","doi":"10.1038/s42255-024-01067-y","DOIUrl":"10.1038/s42255-024-01067-y","url":null,"abstract":"Precision nutrition requires precise tools to monitor dietary habits. Yet current dietary assessment instruments are subjective, limiting our understanding of the causal relationships between diet and health. Biomarkers of food intake (BFIs) hold promise to increase the objectivity and accuracy of dietary assessment, enabling adjustment for compliance and misreporting. Here, we update current concepts and provide a comprehensive overview of BFIs measured in urine and blood. We rank BFIs based on a four-level utility scale to guide selection and identify combinations of BFIs that specifically reflect complex food intakes, making them applicable as dietary instruments. We discuss the main challenges in biomarker development and illustrate key solutions for the application of BFIs in human studies, highlighting different strategies for selecting and combining BFIs to support specific study designs. Finally, we present a roadmap for BFI development and implementation to leverage current knowledge and enable precision in nutrition research. The authors provide an update on the most useful biomarkers in urine and blood for assessing food intake, and delineate strategies that may accelerate the application of biomarkers of food intake for improving human nutritional research.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 8","pages":"1438-1453"},"PeriodicalIF":18.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489612","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}