Nature metabolism最新文献_第8页

Host–microbe interactions rewire metabolism in a C. elegans model of leucine breakdown deficiency 宿主与微生物之间的相互作用重构了秀丽隐杆线虫亮氨酸分解缺乏症模型中的新陈代谢

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-08-08 DOI: 10.1038/s42255-024-01098-5

Yong-Uk Lee, Bennett W. Fox, Rui Guo, Brian J. Curtis, Jingfang Yu, Sookyung Kim, Shivani Nanda, Victor Baumann, L. Safak Yilmaz, Cole M. Haynes, Frank C. Schroeder, Albertha J. M. Walhout

{"title":"Host–microbe interactions rewire metabolism in a C. elegans model of leucine breakdown deficiency","authors":"Yong-Uk Lee, Bennett W. Fox, Rui Guo, Brian J. Curtis, Jingfang Yu, Sookyung Kim, Shivani Nanda, Victor Baumann, L. Safak Yilmaz, Cole M. Haynes, Frank C. Schroeder, Albertha J. M. Walhout","doi":"10.1038/s42255-024-01098-5","DOIUrl":"10.1038/s42255-024-01098-5","url":null,"abstract":"In humans, defects in leucine catabolism cause a variety of inborn errors in metabolism. Here, we use Caenorhabditis elegans to investigate the impact of mutations in mccc-1, an enzyme that functions in leucine breakdown. Through untargeted metabolomic and transcriptomic analyses we find extensive metabolic rewiring that helps to detoxify leucine breakdown intermediates via conversion into previously undescribed metabolites and to synthesize mevalonate, an essential metabolite. We also find that the leucine breakdown product 3,3-hydroxymethylbutyrate (HMB), commonly used as a human muscle-building supplement, is toxic to C. elegans and that bacteria modulate this toxicity. Unbiased genetic screens revealed interactions between the host and microbe, where components of bacterial pyrimidine biosynthesis mitigate HMB toxicity. Finally, upregulated ketone body metabolism genes in mccc-1 mutants provide an alternative route for biosynthesis of the mevalonate precursor 3-hydroxy-3-methylglutaryl-CoA. Our work demonstrates that a complex host–bacteria interplay rewires metabolism to allow host survival when leucine catabolism is perturbed. In a C. elegans model of defective leucine catabolism, Lee et al. analyse how the complex interplay between host and bacteria rewires metabolism to enable host survival.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 8","pages":"1584-1600"},"PeriodicalIF":18.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904471","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

Exploring pancreatic beta-cell subgroups and their connectivity 探索胰腺β细胞亚群及其连接性

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-08-08 DOI: 10.1038/s42255-024-01097-6

Guy A. Rutter, Anne Gresch, Luis Delgadillo Silva, Richard K. P. Benninger

{"title":"Exploring pancreatic beta-cell subgroups and their connectivity","authors":"Guy A. Rutter, Anne Gresch, Luis Delgadillo Silva, Richard K. P. Benninger","doi":"10.1038/s42255-024-01097-6","DOIUrl":"https://doi.org/10.1038/s42255-024-01097-6","url":null,"abstract":"Functional pancreatic islet beta cells are essential to ensure glucose homeostasis across species from zebrafish to humans. These cells show significant heterogeneity, and emerging studies have revealed that connectivity across a hierarchical network is required for normal insulin release. Here, we discuss current thinking and areas of debate around intra-islet connectivity, cellular hierarchies and potential “controlling” beta-cell populations. We focus on methodologies, including comparisons of different cell preparations as well as in vitro and in vivo approaches to imaging and controlling the activity of human and rodent islet preparations. We also discuss the analytical approaches that can be applied to live-cell data to identify and study critical subgroups of cells with a disproportionate role in control Ca2+ dynamics and thus insulin secretion (such as “first responders”, “leaders” and “hubs”, as defined by Ca2+ responses to glucose stimulation). Possible mechanisms by which this hierarchy is achieved, its physiological relevance and how its loss may contribute to islet failure in diabetes mellitus are also considered. A glossary of terms and links to computational resources are provided.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"191 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904494","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

The dual action of basal forebrain in feeding regulation 基底前脑在进食调节中的双重作用

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-08-07 DOI: 10.1038/s42255-024-01111-x

Yu Fu

引用次数: 0

Distinct basal forebrain-originated neural circuits promote homoeostatic feeding and suppress hedonic feeding in male mice 源自前脑基底的不同神经回路可促进雄性小鼠的均衡摄食并抑制享乐性摄食

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-08-07 DOI: 10.1038/s42255-024-01099-4

Hailan Liu, Jonathan C. Bean, Yongxiang Li, Meng Yu, Olivia Z. Ginnard, Kristine M. Conde, Mengjie Wang, Xing Fang, Hesong Liu, Longlong Tu, Na Yin, Junying Han, Yongjie Yang, Qingchun Tong, Benjamin R. Arenkiel, Chunmei Wang, Yang He, Yong Xu

{"title":"Distinct basal forebrain-originated neural circuits promote homoeostatic feeding and suppress hedonic feeding in male mice","authors":"Hailan Liu, Jonathan C. Bean, Yongxiang Li, Meng Yu, Olivia Z. Ginnard, Kristine M. Conde, Mengjie Wang, Xing Fang, Hesong Liu, Longlong Tu, Na Yin, Junying Han, Yongjie Yang, Qingchun Tong, Benjamin R. Arenkiel, Chunmei Wang, Yang He, Yong Xu","doi":"10.1038/s42255-024-01099-4","DOIUrl":"10.1038/s42255-024-01099-4","url":null,"abstract":"Feeding behaviour is influenced by two primary factors: homoeostatic needs driven by hunger and hedonic desires for pleasure even in the absence of hunger. While efficient homoeostatic feeding is vital for survival, excessive hedonic feeding can lead to adverse consequences such as obesity and metabolic dysregulations. However, the neurobiological mechanisms that orchestrate homoeostatic versus hedonic food consumption remain largely unknown. Here we show that GABAergic proenkephalin (Penk) neurons in the diagonal band of Broca (DBB) of male mice respond to food presentation. We further demonstrate that a subset of DBBPenk neurons that project to the paraventricular nucleus of the hypothalamus are preferentially activated upon food presentation during fasting periods and transmit a positive valence to facilitate feeding. On the other hand, a separate subset of DBBPenk neurons that project to the lateral hypothalamus are preferentially activated when detecting a high-fat high-sugar (HFHS) diet and transmit a negative valence to inhibit food consumption. Notably, when given free choice of chow and HFHS diets, mice with the whole DBBPenk population ablated exhibit reduced consumption of chow but increased intake of the HFHS diet, resulting in accelerated development of obesity and metabolic disturbances. Together, we identify a molecularly defined neural population in male mice that is crucial for the maintenance of energy balance by facilitating homoeostatic feeding while suppressing hedonic overeating. The authors identify a neural population in the basal forebrain of mice that is key for maintaining energy balance by facilitating homoeostatic feeding while suppressing hedonic overeating.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 9","pages":"1775-1790"},"PeriodicalIF":18.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899372","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

Metabolic Messengers: itaconate 代谢信使：伊塔康酸

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-07-26 DOI: 10.1038/s42255-024-01092-x

A. F. McGettrick, L. A. Bourner, F. C. Dorsey, L. A. J. O’Neill

引用次数: 0

Non-invasive mapping of brown adipose tissue activity with magnetic resonance imaging 利用磁共振成像对棕色脂肪组织的活动进行无创绘图。

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-07-25 DOI: 10.1038/s42255-024-01082-z

Zimeng Cai, Qiaoling Zhong, Yanqiu Feng, Qian Wang, Zuoman Zhang, Cailv Wei, Zhinan Yin, Changhong Liang, Chong Wee Liew, Lawrence Kazak, Aaron M. Cypess, Zaiyi Liu, Kejia Cai

{"title":"Non-invasive mapping of brown adipose tissue activity with magnetic resonance imaging","authors":"Zimeng Cai, Qiaoling Zhong, Yanqiu Feng, Qian Wang, Zuoman Zhang, Cailv Wei, Zhinan Yin, Changhong Liang, Chong Wee Liew, Lawrence Kazak, Aaron M. Cypess, Zaiyi Liu, Kejia Cai","doi":"10.1038/s42255-024-01082-z","DOIUrl":"10.1038/s42255-024-01082-z","url":null,"abstract":"Thermogenic brown adipose tissue (BAT) has a positive impact on whole-body metabolism. However, in vivo mapping of BAT activity typically relies on techniques involving ionizing radiation, such as [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) and computed tomography (CT). Here we report a noninvasive metabolic magnetic resonance imaging (MRI) approach based on creatine chemical exchange saturation transfer (Cr-CEST) contrast to assess in vivo BAT activity in rodents and humans. In male rats, a single dose of the β3-adrenoceptor agonist (CL 316,243) or norepinephrine, as well as cold exposure, triggered a robust elevation of the Cr-CEST MRI signal, which was consistent with the [18F]FDG PET and CT data and 1H nuclear magnetic resonance measurements of creatine concentration in BAT. We further show that Cr-CEST MRI detects cold-stimulated BAT activation in humans (both males and females) using a 3T clinical scanner, with data-matching results from [18F]FDG PET and CT measurements. This study establishes Cr-CEST MRI as a promising noninvasive and radiation-free approach for in vivo mapping of BAT activity. Creatine chemical exchange saturation transfer magnetic resonance imaging is used successfully to measure brown adipose tissue activity in rats and humans, delivering data that are consistent with [18F]fluorodeoxyglucose PET and CT measurements.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 7","pages":"1367-1379"},"PeriodicalIF":18.9,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759984","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}

引用次数: 0

Microglia mitochondrial complex I deficiency during development induces glial dysfunction and early lethality 小胶质细胞线粒体复合体 I 在发育过程中的缺乏会诱发胶质细胞功能障碍和早期致死率

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-07-24 DOI: 10.1038/s42255-024-01081-0

Bella Mora-Romero, Nicolas Capelo-Carrasco, Juan J. Pérez-Moreno, María I. Alvarez-Vergara, Laura Trujillo-Estrada, Carmen Romero-Molina, Emilio Martinez-Marquez, Noelia Morano-Catalan, Marisa Vizuete, Jose Lopez-Barneo, Jose L. Nieto-Gonzalez, Pablo Garcia-Junco-Clemente, Javier Vitorica, Antonia Gutierrez, David Macias, Alicia E. Rosales-Nieves, Alberto Pascual

{"title":"Microglia mitochondrial complex I deficiency during development induces glial dysfunction and early lethality","authors":"Bella Mora-Romero, Nicolas Capelo-Carrasco, Juan J. Pérez-Moreno, María I. Alvarez-Vergara, Laura Trujillo-Estrada, Carmen Romero-Molina, Emilio Martinez-Marquez, Noelia Morano-Catalan, Marisa Vizuete, Jose Lopez-Barneo, Jose L. Nieto-Gonzalez, Pablo Garcia-Junco-Clemente, Javier Vitorica, Antonia Gutierrez, David Macias, Alicia E. Rosales-Nieves, Alberto Pascual","doi":"10.1038/s42255-024-01081-0","DOIUrl":"10.1038/s42255-024-01081-0","url":null,"abstract":"Primary mitochondrial diseases (PMDs) are associated with pediatric neurological disorders and are traditionally related to oxidative phosphorylation system (OXPHOS) defects in neurons. Interestingly, both PMD mouse models and patients with PMD show gliosis, and pharmacological depletion of microglia, the innate immune cells of the brain, ameliorates multiple symptoms in a mouse model. Given that microglia activation correlates with the expression of OXPHOS genes, we studied whether OXPHOS deficits in microglia may contribute to PMDs. We first observed that the metabolic rewiring associated with microglia stimulation in vitro (via IL-33 or TAU treatment) was partially changed by complex I (CI) inhibition (via rotenone treatment). In vivo, we generated a mouse model deficient for CI activity in microglia (MGcCI). MGcCI microglia showed metabolic rewiring and gradual transcriptional activation, which led to hypertrophy and dysfunction in juvenile (1-month-old) and adult (3-month-old) stages, respectively. MGcCI mice presented widespread reactive astrocytes, a decrease of synaptic markers accompanied by an increased number of parvalbumin neurons, a behavioral deficit characterized by prolonged periods of immobility, loss of weight and premature death that was partially rescued by pharmacologic depletion of microglia. Our data demonstrate that microglia development depends on mitochondrial CI and suggest a direct microglial contribution to PMDs. Microglia rely on mitochondrial complex I during development, suggesting that complex I deficiency in microglia may have a role in primary mitochondrial diseases.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 8","pages":"1479-1491"},"PeriodicalIF":18.9,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755088","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

Complex roles for mitochondrial complexes in microglia 线粒体复合体在小胶质细胞中的复杂作用

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-07-24 DOI: 10.1038/s42255-024-01095-8

Rosa C. Paolicelli, Stefano Pluchino

引用次数: 0

Mitochondrial respiration in microglia is essential for response to demyelinating injury but not proliferation 小胶质细胞的线粒体呼吸对脱髓鞘损伤的反应至关重要，但对增殖并不重要

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-07-24 DOI: 10.1038/s42255-024-01080-1

Joshua S. Stoolman, Rogan A. Grant, Taylor A. Poor, Samuel E. Weinberg, Karis B. D’Alessandro, Jerica Tan, Jennifer Yuan-Shih Hu, Megan E. Zerrer, Walter A. Wood, Madeline C. Harding, Sahil Soni, Karen M. Ridge, Paul T. Schumacker, G. R. Scott Budinger, Navdeep S. Chandel

{"title":"Mitochondrial respiration in microglia is essential for response to demyelinating injury but not proliferation","authors":"Joshua S. Stoolman, Rogan A. Grant, Taylor A. Poor, Samuel E. Weinberg, Karis B. D’Alessandro, Jerica Tan, Jennifer Yuan-Shih Hu, Megan E. Zerrer, Walter A. Wood, Madeline C. Harding, Sahil Soni, Karen M. Ridge, Paul T. Schumacker, G. R. Scott Budinger, Navdeep S. Chandel","doi":"10.1038/s42255-024-01080-1","DOIUrl":"10.1038/s42255-024-01080-1","url":null,"abstract":"Microglia are necessary for central nervous system (CNS) function during development and play roles in ageing, Alzheimer’s disease and the response to demyelinating injury1–5. The mitochondrial respiratory chain (RC) is necessary for conventional T cell proliferation6 and macrophage-dependent immune responses7–10. However, whether mitochondrial RC is essential for microglia proliferation or function is not known. We conditionally deleted the mitochondrial complex III subunit Uqcrfs1 (Rieske iron-sulfur polypeptide 1) in the microglia of adult mice to assess the requirement of microglial RC for survival, proliferation and adult CNS function in vivo. Notably, mitochondrial RC function was not required for survival or proliferation of microglia in vivo. RNA sequencing analysis showed that loss of RC function in microglia caused changes in gene expression distinct from aged or disease-associated microglia. Microglia-specific loss of mitochondrial RC function is not sufficient to induce cognitive decline. Amyloid-β plaque coverage decreased and microglial interaction with amyloid-β plaques increased in the hippocampus of 5xFAD mice with mitochondrial RC-deficient microglia. Microglia-specific loss of mitochondrial RC function did impair remyelination following an acute, reversible demyelinating event. Thus, mitochondrial respiration in microglia is dispensable for proliferation but is essential to maintain a proper response to CNS demyelinating injury. Microglia rely on mitochondrial respiration to respond to demyelinating injury. However, mitochondrial respiration is not required to support microglial proliferation.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 8","pages":"1492-1504"},"PeriodicalIF":18.9,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755087","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

Hydrogen sulfide produced by the gut microbiota impairs host metabolism via reducing GLP-1 levels in male mice 肠道微生物群产生的硫化氢会通过降低雄性小鼠体内的 GLP-1 水平来损害宿主的新陈代谢。

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-07-19 DOI: 10.1038/s42255-024-01068-x

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

{"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}

引用次数: 0