Pub Date : 2026-03-24DOI: 10.1038/s42255-026-01497-w
Amélie Bonnefond, Winter S. Bruner, Struan F. A. Grant, Anita Morandi, Philippe Froguel
{"title":"The genetics of obesity: aetiology, prevention and therapy","authors":"Amélie Bonnefond, Winter S. Bruner, Struan F. A. Grant, Anita Morandi, Philippe Froguel","doi":"10.1038/s42255-026-01497-w","DOIUrl":"https://doi.org/10.1038/s42255-026-01497-w","url":null,"abstract":"","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"190 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506783","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}
Pub Date : 2026-03-23DOI: 10.1038/s42255-026-01476-1
Sun Woo Sophie Kang, Lauryn A. Brown, Colin B. Miller, Katherine M. Barrows, Jihye L. Golino, Hanyang Liu, Constance M. Cultraro, Daniel Feliciano, Mercedes B. Cornelius-Muwanuzi, Kirsten Remmert, Jonathan M. Hernandez, Andy D. Tran, Michael Kruhlak, Alexei Lobanov, Maggie Cam, Natalie Porat-Shliom
Steatotic liver disease is common, yet the mechanisms by which hepatocytes cope with surges in dietary fatty acids remain unclear. Here we use single-cell tissue imaging (scPhenomics) and spatial proteomics to map lipid handling across dietary states. Fasting remodeled mitochondria and lipid droplets (LDs), increasing mitochondria–LD contacts, whereas contacts were infrequent in Western diet (WD)-fed male mice. Fasting also elevated perilipin-5 (PLIN5), a mediator of mitochondria-LD tethering. PLIN5 overexpression modulated contact formation in a phosphorylation-dependent manner: the S155A variant enhanced organelle contacts and LD expansion, whereas the S155E variant reduced contacts and yielded fewer, smaller LDs. Overexpression of the S155A variant in WD reduced lipotoxicity. These data reveal an adaptive organelle-interaction program that channels lipids during nutrient stress and is attenuated by an obesogenic diet. Our work establishes scPhenomics for spatially resolved cell-state analysis and identifies PLIN5 phosphorylation as a lever to tune hepatocyte lipid flux, suggesting therapeutic potential for targeting mitochondria–LD coupling.
{"title":"PLIN5 phosphorylation orchestrates mitochondria lipid-droplet coupling to control hepatic lipid flux and steatosis","authors":"Sun Woo Sophie Kang, Lauryn A. Brown, Colin B. Miller, Katherine M. Barrows, Jihye L. Golino, Hanyang Liu, Constance M. Cultraro, Daniel Feliciano, Mercedes B. Cornelius-Muwanuzi, Kirsten Remmert, Jonathan M. Hernandez, Andy D. Tran, Michael Kruhlak, Alexei Lobanov, Maggie Cam, Natalie Porat-Shliom","doi":"10.1038/s42255-026-01476-1","DOIUrl":"https://doi.org/10.1038/s42255-026-01476-1","url":null,"abstract":"Steatotic liver disease is common, yet the mechanisms by which hepatocytes cope with surges in dietary fatty acids remain unclear. Here we use single-cell tissue imaging (scPhenomics) and spatial proteomics to map lipid handling across dietary states. Fasting remodeled mitochondria and lipid droplets (LDs), increasing mitochondria–LD contacts, whereas contacts were infrequent in Western diet (WD)-fed male mice. Fasting also elevated perilipin-5 (PLIN5), a mediator of mitochondria-LD tethering. PLIN5 overexpression modulated contact formation in a phosphorylation-dependent manner: the S155A variant enhanced organelle contacts and LD expansion, whereas the S155E variant reduced contacts and yielded fewer, smaller LDs. Overexpression of the S155A variant in WD reduced lipotoxicity. These data reveal an adaptive organelle-interaction program that channels lipids during nutrient stress and is attenuated by an obesogenic diet. Our work establishes scPhenomics for spatially resolved cell-state analysis and identifies PLIN5 phosphorylation as a lever to tune hepatocyte lipid flux, suggesting therapeutic potential for targeting mitochondria–LD coupling.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"3 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147496831","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}
Pub Date : 2026-03-23DOI: 10.1038/s42255-026-01483-2
Jessica Segalés,Marc Liesa
{"title":"The expanding role of mitochondria-lipid droplet contacts in liver and their disruption by MASLD.","authors":"Jessica Segalés,Marc Liesa","doi":"10.1038/s42255-026-01483-2","DOIUrl":"https://doi.org/10.1038/s42255-026-01483-2","url":null,"abstract":"","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"47 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502219","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}
Fatty acid (FA) oxidation plays an important role in T cell responses. However, whether DGAT1-mediated FA esterification to triacylglycerol also regulates T cell function remains unclear. Here we uncover a sexually dimorphic requirement for DGAT1 expression in CD8+ tumour-infiltrating lymphocyte function. In female mice, T cell-specific Dgat1 deficiency improves mitochondrial metabolic fitness and expands the pool of progenitor exhausted CD8+ T (Tex) cells to sustain antitumour responses. In male mice, however, Dgat1 deficiency leads to FA peroxidation, endoplasmic reticulum (ER) stress and CD8+ Tex cell death. We show that these effects are mediated by androgen receptor (AR) signalling. Deletion of Ar, overexpression of glutathione peroxidase 4, or inhibition of ER stress-induced cell death rescues Dgat1-deficient CD8+ T cell survival and promotes antitumour responses in male mice. Overall, this study suggests that DGAT1 detoxifies AR signalling in male mice to protect against ER stress-induced cell death and maintain T cell stemness, and uncovers sex-specific metabolic adaptations in the tumour microenvironment.
脂肪酸（FA）氧化在T细胞反应中起着重要作用。然而，dgat1介导的FA酯化成三酰基甘油是否也调节T细胞功能仍不清楚。在这里，我们发现了CD8+肿瘤浸润淋巴细胞功能中DGAT1表达的性别二态要求。在雌性小鼠中，T细胞特异性Dgat1缺陷改善了线粒体代谢适应度，扩大了祖细胞耗尽的CD8+ T （Tex）细胞池，以维持抗肿瘤反应。然而，在雄性小鼠中，Dgat1缺乏导致FA过氧化、内质网（ER）应激和CD8+ Tex细胞死亡。我们发现这些作用是由雄激素受体（AR）信号介导的。Ar的缺失，谷胱甘肽过氧化物酶4的过表达，或内质肽应激诱导的细胞死亡的抑制可以挽救dgat1缺陷的CD8+ T细胞的存活，并促进雄性小鼠的抗肿瘤反应。总体而言，本研究表明，DGAT1可以解毒雄性小鼠的AR信号，以保护内质网应激诱导的细胞死亡和维持T细胞的干细胞性，并揭示肿瘤微环境中性别特异性代谢适应。
{"title":"DGAT1 mediates sex-specific CD8+ T cell antitumour responses.","authors":"Alaa Madi,Hui Shi,Min Su,Ahmed Mady,Boqiong Lv,Haiyan Wang,Bing Yang,Zhenni Yan,Xiaomeng Jin,Lingling Wu,Mengyue Lv,Marvin Hering,Sicong Ma,Alessa Mieg,Ferdinand Zettl,Xin Yan,Kerstin Mohr,Nora Knabe,Gernot Poschet,Karsten Richter,Nikolai Schleußner,Rene-Filip Jackstadt,Sonja Loges,F Nina Papavasiliou,Xi Wang,Jingxia Wu,Guoliang Cui","doi":"10.1038/s42255-026-01462-7","DOIUrl":"https://doi.org/10.1038/s42255-026-01462-7","url":null,"abstract":"Fatty acid (FA) oxidation plays an important role in T cell responses. However, whether DGAT1-mediated FA esterification to triacylglycerol also regulates T cell function remains unclear. Here we uncover a sexually dimorphic requirement for DGAT1 expression in CD8+ tumour-infiltrating lymphocyte function. In female mice, T cell-specific Dgat1 deficiency improves mitochondrial metabolic fitness and expands the pool of progenitor exhausted CD8+ T (Tex) cells to sustain antitumour responses. In male mice, however, Dgat1 deficiency leads to FA peroxidation, endoplasmic reticulum (ER) stress and CD8+ Tex cell death. We show that these effects are mediated by androgen receptor (AR) signalling. Deletion of Ar, overexpression of glutathione peroxidase 4, or inhibition of ER stress-induced cell death rescues Dgat1-deficient CD8+ T cell survival and promotes antitumour responses in male mice. Overall, this study suggests that DGAT1 detoxifies AR signalling in male mice to protect against ER stress-induced cell death and maintain T cell stemness, and uncovers sex-specific metabolic adaptations in the tumour microenvironment.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"14 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490056","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}
Pub Date : 2026-03-20DOI: 10.1038/s42255-026-01469-0
Sarah Zipkowitz,Laura A Sena
{"title":"Fat chance of male and female equality in tumour immunity.","authors":"Sarah Zipkowitz,Laura A Sena","doi":"10.1038/s42255-026-01469-0","DOIUrl":"https://doi.org/10.1038/s42255-026-01469-0","url":null,"abstract":"","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"1 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490062","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}
Pub Date : 2026-03-19DOI: 10.1038/s42255-026-01485-0
Shuke Xiao, Mengjie Wang, Thomas G Martin, Barry Scott, Xing Fang, Xinming Liu, Yongjie Yang, Sipei Fu, Steven D Truong, Jack F Gugel, Gregory L Maas, Marcus P Mullen, Jennifer Hampton Hill, Veronica L Li, Andrew L Markhard, Mingming Zhao, Wei Qi, Saranya C Reghupaty, Meng Zhao, Jan Spaas, Wei Wei, Trine Moholdt, John A Hawley, Christian T Voldstedlund, Erik A Richter, Xiaoke Chen, Katrin J Svensson, Daniel Bernstein, Leslie A Leinwand, Yong Xu, Jonathan Z Long
Most mammals consume small and frequent meals. By contrast, pythons are ambush predators that exhibit extreme feeding and fasting patterns and provide a unique model for uncovering molecular mediators of the postprandial response1-3. Using untargeted metabolomics, we show that circulating levels of the metabolite para-tyramine-O-sulphate (pTOS) are increased more than 1,000-fold in pythons after a single meal. In pythons, pTOS production occurs in a microbiome-dependent manner via sequential decarboxylation and sulphation of dietary tyrosine. In both pythons and mice, pTOS administration activates a neural population in the ventromedial hypothalamus (VMH). In mice, these VMH neurons are required for the anorexigenic effects of pTOS. Chronic administration of pTOS to diet-induced obese male mice suppresses food intake and body weight. pTOS is also present in human blood, where its levels are increased after a meal. Together, these data uncover a conserved postprandial anorexigenic metabolite that links nutrient intake to energy balance.
大多数哺乳动物进食少而频繁。相比之下，蟒蛇是埋伏捕食者，表现出极端的进食和禁食模式，为揭示餐后反应的分子介质提供了一个独特的模型。使用非靶向代谢组学，我们发现在一顿饭后，蟒蛇的代谢物对酪胺- o -硫酸盐（pTOS）的循环水平增加了1000多倍。在蟒蛇中，pTOS的产生以微生物依赖的方式发生，通过连续的脱羧和膳食酪氨酸的磺化。在蟒蛇和小鼠中，pTOS管理激活下丘脑腹内侧（VMH）的神经群。在小鼠中，这些VMH神经元是pTOS厌氧性作用所必需的。长期给药pTOS抑制饮食诱导的肥胖雄性小鼠的食物摄入量和体重。pTOS也存在于人体血液中，其水平在餐后升高。总之，这些数据揭示了一种保守的餐后无氧代谢物，它将营养摄入与能量平衡联系起来。
{"title":"Python metabolomics uncovers a conserved postprandial metabolite and gut-brain feeding pathway.","authors":"Shuke Xiao, Mengjie Wang, Thomas G Martin, Barry Scott, Xing Fang, Xinming Liu, Yongjie Yang, Sipei Fu, Steven D Truong, Jack F Gugel, Gregory L Maas, Marcus P Mullen, Jennifer Hampton Hill, Veronica L Li, Andrew L Markhard, Mingming Zhao, Wei Qi, Saranya C Reghupaty, Meng Zhao, Jan Spaas, Wei Wei, Trine Moholdt, John A Hawley, Christian T Voldstedlund, Erik A Richter, Xiaoke Chen, Katrin J Svensson, Daniel Bernstein, Leslie A Leinwand, Yong Xu, Jonathan Z Long","doi":"10.1038/s42255-026-01485-0","DOIUrl":"10.1038/s42255-026-01485-0","url":null,"abstract":"<p><p>Most mammals consume small and frequent meals. By contrast, pythons are ambush predators that exhibit extreme feeding and fasting patterns and provide a unique model for uncovering molecular mediators of the postprandial response<sup>1-3</sup>. Using untargeted metabolomics, we show that circulating levels of the metabolite para-tyramine-O-sulphate (pTOS) are increased more than 1,000-fold in pythons after a single meal. In pythons, pTOS production occurs in a microbiome-dependent manner via sequential decarboxylation and sulphation of dietary tyrosine. In both pythons and mice, pTOS administration activates a neural population in the ventromedial hypothalamus (VMH). In mice, these VMH neurons are required for the anorexigenic effects of pTOS. Chronic administration of pTOS to diet-induced obese male mice suppresses food intake and body weight. pTOS is also present in human blood, where its levels are increased after a meal. Together, these data uncover a conserved postprandial anorexigenic metabolite that links nutrient intake to energy balance.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":" ","pages":""},"PeriodicalIF":20.8,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486789","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}
Pub Date : 2026-03-18DOI: 10.1038/s42255-026-01484-1
Melanie Picot,Nesrine Hifdi,Mathilde Vaucourt,Melanie Mansat,Peng Li,Isabel Singer,Gaëtan Chicanne,Alexandre Stella,Shen Kuang,Caterina Miceli,Nathaniel F Henneman,Bernard Payrastre,Marie Vandromme,Odile Schiltz,Ivan Nemazanyy,Mariana E G de Araujo,Ganna Panasyuk,Julien Viaud,Michael Lämmerhofer,Karim Hnia
Lysosomes act as metabolic signalling hubs that integrate nutrient availability to coordinate anabolic and catabolic programmes. Mechanistic target of rapamycin complex 1 (mTORC1) is activated at the lysosomal surface by amino acids through RagGTPases recruited by the lysosomal adaptor and MAPK and mTOR activator complex, yet the contribution of lysosomal lipid composition to this pathway remains unclear. Here we identify lysosomal phosphoinositides, PI3P and PI(3,5)P2, as key regulators of lysosomal adaptor and MAPK and mTOR activator complex stability and dynamics at the lysosome. These lipid pools are controlled by the phosphoinositide 3-phosphatase MTM1, mutated in myotubular myopathy, via endoplasmic reticulum-lysosome membrane contact sites. Under endoplasmic reticulum stress, MTM1-dependent phosphoinositide remodelling suppresses RagGTPase-mTORC1 signalling, thereby regulating anabolic-catabolic balance during myogenic differentiation. Restoring mTORC1 activity or lysosomal phosphoinositide homeostasis rescues Rag-dependent signalling and muscle growth in cellular and mouse models of myopathy, uncovering a lysosome-centred metabolic checkpoint with direct disease relevance.
{"title":"Lysosomal phosphoinositide turnover acts upstream of RagGTPase-mTORC1 and controls muscle growth.","authors":"Melanie Picot,Nesrine Hifdi,Mathilde Vaucourt,Melanie Mansat,Peng Li,Isabel Singer,Gaëtan Chicanne,Alexandre Stella,Shen Kuang,Caterina Miceli,Nathaniel F Henneman,Bernard Payrastre,Marie Vandromme,Odile Schiltz,Ivan Nemazanyy,Mariana E G de Araujo,Ganna Panasyuk,Julien Viaud,Michael Lämmerhofer,Karim Hnia","doi":"10.1038/s42255-026-01484-1","DOIUrl":"https://doi.org/10.1038/s42255-026-01484-1","url":null,"abstract":"Lysosomes act as metabolic signalling hubs that integrate nutrient availability to coordinate anabolic and catabolic programmes. Mechanistic target of rapamycin complex 1 (mTORC1) is activated at the lysosomal surface by amino acids through RagGTPases recruited by the lysosomal adaptor and MAPK and mTOR activator complex, yet the contribution of lysosomal lipid composition to this pathway remains unclear. Here we identify lysosomal phosphoinositides, PI3P and PI(3,5)P2, as key regulators of lysosomal adaptor and MAPK and mTOR activator complex stability and dynamics at the lysosome. These lipid pools are controlled by the phosphoinositide 3-phosphatase MTM1, mutated in myotubular myopathy, via endoplasmic reticulum-lysosome membrane contact sites. Under endoplasmic reticulum stress, MTM1-dependent phosphoinositide remodelling suppresses RagGTPase-mTORC1 signalling, thereby regulating anabolic-catabolic balance during myogenic differentiation. Restoring mTORC1 activity or lysosomal phosphoinositide homeostasis rescues Rag-dependent signalling and muscle growth in cellular and mouse models of myopathy, uncovering a lysosome-centred metabolic checkpoint with direct disease relevance.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"44 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478899","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}
Accurate measurement of dietary intake remains a cornerstone challenge in optimizing the efficacy of nutritional interventions in human disease. Traditional self-reporting methods, although scalable and widely used, are prone to major bias and measurement error, thereby limiting their precision and clinical utility. In this Review, we highlight recent advances in technology-assisted food intake measurement, including image-based logging, wearable sensors and artificial intelligence (AI)-based dietary estimation, which may reduce reliance on recall and improve intake estimation. We review the emergence of non-invasive biological methodologies, such as metagenome-informed metaproteomics, in accurately enabling objective measurement of food intake and nutrient digestion and absorption in molecular resolution. We explore the possible interactions and effects of the gut microbiome in modulating such person-specific digestive and absorptive patterns and discuss challenges and prospects in the convergence of omics-based, measurement-based and AI-based dietary assessment tools into precision nutrition, in fulfilling its immense potential towards optimization of patient care.
{"title":"Advances and opportunities in measuring dietary intake: from omics to AI.","authors":"Yotam Cohen,Tallulah Jansen,Serena Onwuka,Eran Elinav","doi":"10.1038/s42255-026-01494-z","DOIUrl":"https://doi.org/10.1038/s42255-026-01494-z","url":null,"abstract":"Accurate measurement of dietary intake remains a cornerstone challenge in optimizing the efficacy of nutritional interventions in human disease. Traditional self-reporting methods, although scalable and widely used, are prone to major bias and measurement error, thereby limiting their precision and clinical utility. In this Review, we highlight recent advances in technology-assisted food intake measurement, including image-based logging, wearable sensors and artificial intelligence (AI)-based dietary estimation, which may reduce reliance on recall and improve intake estimation. We review the emergence of non-invasive biological methodologies, such as metagenome-informed metaproteomics, in accurately enabling objective measurement of food intake and nutrient digestion and absorption in molecular resolution. We explore the possible interactions and effects of the gut microbiome in modulating such person-specific digestive and absorptive patterns and discuss challenges and prospects in the convergence of omics-based, measurement-based and AI-based dietary assessment tools into precision nutrition, in fulfilling its immense potential towards optimization of patient care.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"20 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478898","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}
Pub Date : 2026-03-12DOI: 10.1038/s42255-026-01475-2
Ibrahim AlZaim, Mohamed N. Hassan, Maja Schröter, Luca Mannino, Katarina Dragicevic, Marie Balle Sjogaard, Joseph Festa, Lolita Dokshokova, Sophie Weinbrenner, Blanca Tardajos Ayllon, Bettina Hansen, Rikke Kongsgaard Rasmussen, Julie N. Christensen, Olivia Wagman, Ruby Schipper, Min Cai, Wouter Dheedene, Anja Bille Bohn, Jean Farup, Lin Lin, Samuele Soraggi, Anna Dalsgaard Thorsen, Amanda Bæk, Henrik Holm Thomsen, Maximilian von Heesen, Lena-Christin Conradi, Paul Evans, Carolina E. Hagberg, Joerg Heeren, Margo Emont, Evan D. Rosen, Aernout Luttun, Anders Etzerodt, Lucas Massier, Mikael Rydén, Niklas Mejhert, Matthias Blüher, Konstantin Khodosevich, Robert A. Fenton, Bilal N. Sheikh, Niels Jessen, Laura P.M.H. de Rooij, Joanna Kalucka
Adipose tissue homeostasis depends on an intact vascular network that ensures adequate nutrient delivery and immune regulation. In obesity, vascular dysfunction, particularly within endothelial cells (ECs), contributes to inflammation and metabolic disease progression, yet the cellular organization of the human adipose vasculature remains poorly defined. Here we show, using single-cell RNA sequencing of nearly 70,000 vascular cells from human subcutaneous adipose tissue of 65 individuals, that the adipose vasculature is highly heterogeneous and consists of seven canonical EC subtypes. In addition, we identify a distinct population of ECs that display mixed endothelial, mesenchymal, adipocytic and immune transcriptional features. Computational analyses and whole-mount imaging support their presence and suggest that they emerge through endothelial-to-mesenchymal transition. Comparative analyses further reveal inflammatory and fibrotic vascular signatures in obesity and type 2 diabetes. Together, this atlas delineates the cellular complexity of the human adipose vasculature and highlights its contribution to metabolic disease.
{"title":"Defining the vascular niche of human adipose tissue across metabolic states","authors":"Ibrahim AlZaim, Mohamed N. Hassan, Maja Schröter, Luca Mannino, Katarina Dragicevic, Marie Balle Sjogaard, Joseph Festa, Lolita Dokshokova, Sophie Weinbrenner, Blanca Tardajos Ayllon, Bettina Hansen, Rikke Kongsgaard Rasmussen, Julie N. Christensen, Olivia Wagman, Ruby Schipper, Min Cai, Wouter Dheedene, Anja Bille Bohn, Jean Farup, Lin Lin, Samuele Soraggi, Anna Dalsgaard Thorsen, Amanda Bæk, Henrik Holm Thomsen, Maximilian von Heesen, Lena-Christin Conradi, Paul Evans, Carolina E. Hagberg, Joerg Heeren, Margo Emont, Evan D. Rosen, Aernout Luttun, Anders Etzerodt, Lucas Massier, Mikael Rydén, Niklas Mejhert, Matthias Blüher, Konstantin Khodosevich, Robert A. Fenton, Bilal N. Sheikh, Niels Jessen, Laura P.M.H. de Rooij, Joanna Kalucka","doi":"10.1038/s42255-026-01475-2","DOIUrl":"https://doi.org/10.1038/s42255-026-01475-2","url":null,"abstract":"Adipose tissue homeostasis depends on an intact vascular network that ensures adequate nutrient delivery and immune regulation. In obesity, vascular dysfunction, particularly within endothelial cells (ECs), contributes to inflammation and metabolic disease progression, yet the cellular organization of the human adipose vasculature remains poorly defined. Here we show, using single-cell RNA sequencing of nearly 70,000 vascular cells from human subcutaneous adipose tissue of 65 individuals, that the adipose vasculature is highly heterogeneous and consists of seven canonical EC subtypes. In addition, we identify a distinct population of ECs that display mixed endothelial, mesenchymal, adipocytic and immune transcriptional features. Computational analyses and whole-mount imaging support their presence and suggest that they emerge through endothelial-to-mesenchymal transition. Comparative analyses further reveal inflammatory and fibrotic vascular signatures in obesity and type 2 diabetes. Together, this atlas delineates the cellular complexity of the human adipose vasculature and highlights its contribution to metabolic disease.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"26 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147394039","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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