Nature metabolism最新文献

{"title":"Cold sensing and the parabrachial nucleus","authors":"Óscar Freire-Agulleiro, Miguel López","doi":"10.1038/s42255-026-01571-3","DOIUrl":"10.1038/s42255-026-01571-3","url":null,"abstract":"The neural mechanisms integrating cold sensory input with adaptive thermoregulation remain incompletely understood. A new study published in Nature Metabolism identifies cold-activated neurons in the parabrachial nucleus as recipients of cold sensory cues, which coordinate autonomic, metabolic and behavioural cold responses and act as therapeutic targets for metabolic disorders.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 8","pages":"1627-1628"},"PeriodicalIF":27.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765263","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: The perineurium integrates leptin with its sympathetic outflow to protect against obesity","authors":"Gitalee Sarker, Emma Haberman, Anandhakumar Chandran, Thomas Monfeuga, Cyrielle Maroteau, Sofia Lundh, David S. Oliveira, Andrea Raimondi, Karin Ziegler, Tiago Gomes, Tiago N. Cordeiro, Karishma Parekh, Emilia Schmid, Paola Fernández-Sanmartín, Alina Griebel, Noelia Martinez-Sanchez, Bernardo A. Arús, Samson W. Cheung, Yitao Zhu, Michal Shaked, Sarah C. L. Knowles, Stefan Hanns Engelhardt, Matteo Iannacone, Philipp E. Scherer, Miguel López, Enrique M. Toledo, Ana I. Domingos","doi":"10.1038/s42255-026-01605-w","DOIUrl":"10.1038/s42255-026-01605-w","url":null,"abstract":"","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 9","pages":"1-1"},"PeriodicalIF":27.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-026-01605-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713290","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":"Career pathways, part 20","authors":"Adelheid Lempradl, Lauren V. Albrecht","doi":"10.1038/s42255-026-01596-8","DOIUrl":"10.1038/s42255-026-01596-8","url":null,"abstract":"Academic careers are shaped by scientific discovery, professional networks, mentorship and the challenges of balancing research with personal and professional responsibilities. In this instalment of our Career Pathways series, Adelheid (Heidi) Lempradl and Lauren V. Albrecht share their experiences of building independent research careers and navigating the opportunities and challenges of academia.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 9","pages":"1-3"},"PeriodicalIF":27.5,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689718","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":"Palmitoylation modulates neutrophil anti-tumour function in liver metastasis","authors":"Liang Zhou, Jun Cui","doi":"10.1038/s42255-026-01581-1","DOIUrl":"10.1038/s42255-026-01581-1","url":null,"abstract":"How liver metastases evade immunity remains unclear. A new study published in Nature Metabolism reveals that DHHC17-driven laminin 511 palmitoylation and its subsequent secretion blunts neutrophil-mediated killing of metastatic cancer cells, uncovering a druggable immune checkpoint in the liver.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 8","pages":"1631-1632"},"PeriodicalIF":27.5,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679495","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":"Palmitate promotes liver metastases by decreasing neutrophil antitumour behaviour","authors":"Anke Vandekeere, Juan Fernández-García, Yiming Peng-Winkler, Miguel Martín Pérez, Ming Liu, Sara Isabel Fernandes, Janine Theile, Philipp Willnow, Sanne Verheul, Gitte Zels, Anirudh Pabba, Christine Desmedt, Cornelis Verhoef, Patricia Altea-Manzano, Salvador Aznar Benitah, Ilaria Elia, Ilaria Malanchi, Sarah-Maria Fendt","doi":"10.1038/s42255-026-01582-0","DOIUrl":"10.1038/s42255-026-01582-0","url":null,"abstract":"Liver metastases are frequent and challenging to treat owing to the liver’s metabolically active and immune-tolerant environment. However, how cancer cells exploit nutrient availability in the liver to evade immune surveillance remains unknown. Here we show that cancer cells use the palmitate availability in the liver to impair the neutrophil antitumour function. Mechanistically, we find that breast and colorectal cancer cells metastasizing to the liver, but not the lung, require the palmitoyltransferase 17 (DHHC17, gene name ZDHHC17) to stabilize laminin-511 enabling its secretion. In turn, neutrophils in the liver metastasis environment respond to laminin-511 by decreasing their cancer cell-killing capacity. Consistently, silencing ZDHHC17 in cancer cells decreases liver metastases only in the presence of neutrophils, while metastasis growth is restored in ZDHHC17-silenced metastases upon injection of laminin-511 or inhibition of neutrophil degranulation. Taken together, we find that liver palmitate not only supports tumour intrinsic processes but also enables immune evasion. DHHC17-mediated palmitoylation promotes laminin-511 stabilization and availability in the liver metastatic niche, which decreases the cancer cell-killing capacity of neutrophils.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 8","pages":"1730-1750"},"PeriodicalIF":27.5,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679438","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: p21-activated kinase 4 counteracts PKA-dependent lipolysis by phosphorylating FABP4 and HSL","authors":"Hwang Chan Yu, Yong Geun Jeon, Ann-Yae Na, Chang Yeob Han, Mi Rin Lee, Jae Do Yang, Hee Chul Yu, Jung Beom Son, Nam Doo Kim, Jae Bum Kim, Sangkyu Lee, Eun Ju Bae, Byung-Hyun Park","doi":"10.1038/s42255-026-01597-7","DOIUrl":"10.1038/s42255-026-01597-7","url":null,"abstract":"","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 9","pages":"2036-2036"},"PeriodicalIF":27.5,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-026-01597-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648929","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":"Short-chain fatty acids","authors":"Aygul Dagbasi, Mingzhu Cai, Aanya Hirdaramani, Aylin Hanyaloglu, Douglas J. Morrison, Gary Frost","doi":"10.1038/s42255-026-01579-9","DOIUrl":"10.1038/s42255-026-01579-9","url":null,"abstract":"Short-chain fatty acids (SCFAs), principally acetate, propionate and butyrate, are produced by the gut microbiota through the fermentation of non-digestible carbohydrates. Beyond serving as energy substrates, SCFAs act as signalling molecules that influence metabolism, immune function and physiological homeostasis across multiple organ systems. This Review consolidates the fragmented literature on SCFAs and provides an overview of their production, metabolism and physiological actions. We discuss the microbial and dietary determinants of SCFA production, including the roles of the gut microbiome, cross-feeding interactions and dietary carbohydrates. We then examine the mechanisms through which SCFAs exert their effects, focusing on receptor-mediated signalling, epigenetic regulation and tissue-specific physiological functions. Finally, we evaluate the current evidence linking SCFAs to metabolic health and disease and consider the translational potential of targeting SCFA pathways through dietary and therapeutic approaches. At a time when inadequate dietary fibre intake is a growing public health concern, this Review highlights the physiological importance of SCFAs and their potential role in metabolic health and disease prevention. This Review provides an overview of the biology of short-chain fatty acids, with a focus on their synthesis, signalling and physiological effects, highlighting their translational potential for metabolic and inflammatory diseases.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 8","pages":"1652-1668"},"PeriodicalIF":27.5,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620527","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":"Microbial catalysts unlock vitamin bioproduction","authors":"Alejandro I. Ramirez, Lukas Ernst, Jay D. Keasling","doi":"10.1038/s42255-026-01584-y","DOIUrl":"10.1038/s42255-026-01584-y","url":null,"abstract":"The sustainable production of vitamin E in microbial cell factories has been restricted to tocotrienol derivatives. In this issue of Nature Metabolism, Zhang, Li and Cao et al. leverage non-classical enzymatic catalysts that are endogenous to Rhodobacter species to engineer a microbial chassis that produces tocopherols at gram scale.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 8","pages":"1636-1637"},"PeriodicalIF":27.5,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605609","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":"A non-classical biosynthetic route enables tocopherol synthesis in bacteria","authors":"Yang Zhang, Zhizhen Li, Lichuang Cao, Yan Wang, Junyi Wang, Haofeng Chen, Wenhao Li, Xinyu Gao, Qingchen Li, Zhengxin Chen, Kaixuan Xu, Xiangpeng Yang, Xiangrui Wu, Jintao Luo, Jianzhong Liu, Jifeng Yuan","doi":"10.1038/s42255-026-01576-y","DOIUrl":"10.1038/s42255-026-01576-y","url":null,"abstract":"Tocopherols have been widely applied in healthcare, medicine, animal feed and other fields. However, microbial synthesis of tocopherols with industrial potential has not been accomplished yet. Here we report a non-classical biosynthetic route for tocopherol synthesis in Rhodobacter species that bypasses the classical α-tocopherol pathway requiring the 2,3-dimethyl-5-phytyl-1,4-benzoquinone (DMPBQ) as an intermediate. In particular, a Rhodobacter methyltransferase with bifunctional γ/β-tocopherol methyltransferase activities is identified, which can directly synthesize α-tocopherol from δ-tocopherol and γ/β-tocopherols. Furthermore, geranylgeranyl pyrophosphate reductase (GR) plays an important role in reducing tocotrienols into tocopherols. Through systematic metabolic engineering, the engineered Rhodobacter sphaeroides produced a total titer of 508.21 mg l−1 tocopherols in shake flasks, and 3.51 g l−1 under the fed-batch fermentation after process optimization. Taken together, these results offer a non-classical biosynthetic pathway for efficient tocopherol biosynthesis, which would pave the way for future commercial production of tocopherols by microbial fermentation. The study reports a non-classical tocopherol pathway in Rhodobacter that enables heterologous α-tocopherol synthesis by bypassing DMPBQ via a γ/β-tocopherol methyltransferase.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 8","pages":"1805-1817"},"PeriodicalIF":27.5,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605533","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":"Distinct brain regions mediate regulation of food intake in response to GIPR agonism or antagonism","authors":"Jo Edward Lewis, Mireia Montaner, Danae Nuzzaci, Paula-Peace James-Okoro, Norio Harada, Nobuya Inagaki, W. Scott Dodson, Patrick J. Knerr, Jonathan D. Douros, Fiona Mary Gribble, Frank Reimann","doi":"10.1038/s42255-026-01575-z","DOIUrl":"10.1038/s42255-026-01575-z","url":null,"abstract":"The development of dual agonists for the glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) has been a landmark moment in the treatment of type 2 diabetes and obesity. However, for reasons that are incompletely understood, in preclinical and clinical studies, adding either a GIPR agonist or GIPR antagonist to GLP-1R agonism causes additional weight loss1. Here we show that distinct brain regions mediate the appetite-suppressing effects of GIPR agonists and the synergistic weight loss effects conferred by GIPR antagonists. We knock out Gipr in either the area postrema (AP) or hypothalamus of mice (GiprAP-KO and Giprhypo-KO, respectively) and compare body weight and food intake responses to GIPR agonists and antagonists, alone and in combination with the GLP-1R agonist liraglutide. GiprAP-KO mice exhibit partial protection against diet-induced obesity, reduced responsiveness to the appetite-suppressing effects of acyl-GIP and a reduced ability of acyl-GIP to prevent avoidance triggered by peptide YY. Weight loss effects of liraglutide are comparable in GiprAP-KO and control mice, and the co-administration of a GIPR antagonist peptide causes similar additional weight loss in both groups. Giprhypo-KO mice, by contrast, exhibit normal appetite suppression by acyl-GIP but enhanced weight loss on liraglutide compared with control mice. Giprhypo-KO also abolishes the synergistic effect of a GIPR antagonist when combined with liraglutide—an effect that is not mediated by nucleus tractus solitarius preproglucagon neurons. GIPR antagonism and Giprhypo-KO also sensitise to cagrilintide-induced weight loss. Overall, our results suggest that the AP is responsible for the appetite-suppressing effects of GIPR agonism but that GIP receptors in the hypothalamus underlie the ability of GIPR antagonism to enhance the weight loss effects of GLP-1R and amylin receptor agonists. The study employs region-specific knockout of the glucose-dependent insulinotropic polypeptide receptor (GIPR) in either the area postrema or hypothalamus of mice to determine how GIPR agonism and antagonism regulate food intake and body weight via distinct brain regions.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 8","pages":"1669-1678"},"PeriodicalIF":27.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-026-01575-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148585037","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}