Nature metabolism最新文献

{"title":"Hydrogen sulfide produced by the gut microbiota impairs host metabolism via reducing GLP-1 levels in male mice","authors":"Qingqing Qi, Huijie Zhang, Zheyu Jin, Changchun Wang, Mengyu Xia, Bandy Chen, Bomin Lv, Ludmila Peres Diaz, Xue Li, Ru Feng, Mengdi Qiu, Yang Li, David Meseguer, Xiaojiao Zheng, Wei Wang, Wei Song, He Huang, Hao Wu, Lei Chen, Marc Schneeberger, Xiaofei Yu","doi":"10.1038/s42255-024-01068-x","DOIUrl":"10.1038/s42255-024-01068-x","url":null,"abstract":"Dysbiosis of the gut microbiota has been implicated in the pathogenesis of metabolic syndrome (MetS) and may impair host metabolism through harmful metabolites. Here, we show that Desulfovibrio, an intestinal symbiont enriched in patients with MetS, suppresses the production of the gut hormone glucagon-like peptide 1 (GLP-1) through the production of hydrogen sulfide (H2S) in male mice. Desulfovibrio-derived H2S is found to inhibit mitochondrial respiration and induce the unfolded protein response in intestinal L cells, thereby hindering GLP-1 secretion and gene expression. Remarkably, blocking Desulfovibrio and H2S with an over-the-counter drug, bismuth subsalicylate, improves GLP-1 production and ameliorates diet-induced metabolic disorder in male mice. Together, our study uncovers that Desulfovibrio-derived H2S compromises GLP-1 production, shedding light on the gut-relayed mechanisms by which harmful microbiota-derived metabolites impair host metabolism in MetS and suggesting new possibilities for treating MetS. The intestinal symbiont Desulfovibrio, which is enriched in individuals with metabolic syndrome, is found to suppress the production of GLP-1 in male mice. The over-the-counter drug bismuth subsalicylate inhibits the effect of Desulfovibrio and restores GLP-1 levels.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 8","pages":"1601-1615"},"PeriodicalIF":18.9,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727550","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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"title":"Author Correction: ASS1 metabolically contributes to the nuclear and cytosolic p53-mediated DNA damage response","authors":"Lisha Qiu Jin Lim, Lital Adler, Emma Hajaj, Leandro R. Soria, Rotem Ben-Tov Perry, Naama Darzi, Ruchama Brody, Noa Furth, Michal Lichtenstein, Elizabeta Bab-Dinitz, Ziv Porat, Tevie Melman, Alexander Brandis, Sergey Malitsky, Maxim Itkin, Yael Aylon, Shifra Ben-Dor, Irit Orr, Amir Pri-Or, Rony Seger, Yoav Shaul, Eytan Ruppin, Moshe Oren, Minervo Perez, Jordan Meier, Nicola Brunetti-Pierri, Efrat Shema, Igor Ulitsky, Ayelet Erez","doi":"10.1038/s42255-024-01090-z","DOIUrl":"10.1038/s42255-024-01090-z","url":null,"abstract":"","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 7","pages":"1417-1417"},"PeriodicalIF":18.9,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534786","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}

{"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}

{"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}

{"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}