Nature metabolism最新文献_第6页

Neutrophil serine proteases inhibit thermogenic capacity of visceral white adipose tissue 中性粒细胞丝氨酸蛋白酶抑制内脏白色脂肪组织的产热能力。

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-08-31 DOI: 10.1038/s42255-026-01598-6

Lufengzi Yuan, Xiaoping Wu, Jiuyu Zong, Mengxue Jiang, Sanxing Gao, Zixuan Zhang, Xiaowen Huang, Manyu Zhu, Minqi Xiang, Lin Wang, Zhihui Ping, Yong Pan, Dewei Ye, Aimin Xu, Ruby Lai Chong Hoo

{"title":"Neutrophil serine proteases inhibit thermogenic capacity of visceral white adipose tissue","authors":"Lufengzi Yuan, Xiaoping Wu, Jiuyu Zong, Mengxue Jiang, Sanxing Gao, Zixuan Zhang, Xiaowen Huang, Manyu Zhu, Minqi Xiang, Lin Wang, Zhihui Ping, Yong Pan, Dewei Ye, Aimin Xu, Ruby Lai Chong Hoo","doi":"10.1038/s42255-026-01598-6","DOIUrl":"10.1038/s42255-026-01598-6","url":null,"abstract":"Neutrophils and neutrophil-derived serine proteases (NSPs), including neutrophil elastase (NE) and proteinase 3 (PR3), are present in visceral fat of individuals and rodents with obesity, yet their roles in energy metabolism remain elusive. Here we show that neutrophil infiltration and NSP activation impair visceral fat browning in response to β-adrenergic receptor stimulation or cold exposure in male mice. Genetic deletion or local pharmacological inhibition of NE with sivelestat rescued visceral fat browning and enhanced thermogenesis. Mechanistically, NE/PR3 directly suppresses beige adipogenesis by arresting cell cycle via CDK4/cyclin D1 downregulation, impairs beige adipocyte differentiation by degrading insulin-like growth factor binding protein-3, and indirectly promotes M1 macrophage polarization. Administration of sivelestat suppressed diet-induced neutrophil infiltration, enhanced cold-induced visceral fat browning and decreased visceral fat content in mice. These findings reveal an unexpected inhibitory role of NSPs in visceral fat browning and suggest the potential of repurposing sivelestat as an anti-obese drug. Neutrophil infiltration and neutrophil serine protease activation regulates visceral fat browning and thermogenic activity during cold exposure in male mice.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 9","pages":"1971-1989"},"PeriodicalIF":27.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866029","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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A brief guide to the identification and characterization of secreted molecules 一个简单的指南，以鉴定和表征分泌分子。

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-08-31 DOI: 10.1038/s42255-026-01607-8

Avinash D. Londhe, Niels B. Danneskiold-Samsøe, Katrin J. Svensson

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Neutrophil proteases put the brakes on visceral beiging 中性粒细胞蛋白酶抑制了内脏变脏。

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-08-31 DOI: 10.1038/s42255-026-01606-9

Marcus J. Tol, Rinke Stienstra

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Multi-organ proteomic atlas of obesity regression in male mice 雄性小鼠肥胖消退的多器官蛋白质组学图谱

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-08-21 DOI: 10.1038/s42255-026-01599-5

Felix Boel, Ellen Gammelmark Klinggaard, Vyacheslav Akimov, Daniel Hansen, M. L. Uthpala, Babukrishna Maniyadath, Flora Reincke Fuglsang, Marc Pielies Avellí, Simon Rasmussen, Kim Ravnskjær, Susanne Mandrup, Blagoy Blagoev

{"title":"Multi-organ proteomic atlas of obesity regression in male mice","authors":"Felix Boel, Ellen Gammelmark Klinggaard, Vyacheslav Akimov, Daniel Hansen, M. L. Uthpala, Babukrishna Maniyadath, Flora Reincke Fuglsang, Marc Pielies Avellí, Simon Rasmussen, Kim Ravnskjær, Susanne Mandrup, Blagoy Blagoev","doi":"10.1038/s42255-026-01599-5","DOIUrl":"10.1038/s42255-026-01599-5","url":null,"abstract":"Obesity drives systemic metabolic dysfunction, yet how the body adapts and recovers at a system-wide level remains unclear. Here we generate a multi-organ proteomic atlas of diet-induced obesity and its regression in male mice. Using a standardized, semi-automated sample preparation workflow, we quantify 12,936 unique proteins across 15 organs and four timepoints. We find proteomic changes to be highly tissue-dependent, with a small number of proteins displaying shared changes across multiple tissues. While proteomes of most tissues revert to lean levels after weight loss, white adipose tissue retains strong phagocytic and inflammatory responses, and the brain, kidney, bone, thymus and spleen display delayed obesity-induced alterations. We map the adipose tissue-specific immune regulators using ligand-target inference and show reduced expression of proteasomal subunits in brown adipose tissue, resulting in stalled ubiquitin turnover. Finally, we make all datasets open access and create an interactive webtool to facilitate further community-driven discovery. A multi-organ proteomics resource of diet-induced obesity and its regression in male mice, spanning 15 organs and 4 timepoints, highlights systemic changes as well as impairments in adipose tissue function even under weight loss conditions.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 9","pages":"2023-2034"},"PeriodicalIF":27.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148769291","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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A proteomic atlas of obesity and weight loss 肥胖和减肥的蛋白质组图谱。

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-08-21 DOI: 10.1038/s42255-026-01601-0

Natasha D. Suriani, Matthew J. Watt

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Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism 异亮氨酸和缬氨酸通过丙酰辅酶a介导的胆固醇代谢促进前列腺癌的进展

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-08-20 DOI: 10.1038/s42255-026-01583-z

Zhongchi Li, Shuchen Liu, Wenbing Jin, Leyi Xiao, Olivia Kester, Nayah Bullen, Xuanrong Chen, Un In Chan, Jude Owiredu, Zhucui Li, Rabia Khan, Jennifer Endress, Moniquetta Shafer, Vivien Low, Nikolaos Koundouros, Sungyun Cho, Christopher Barbieri, Chun-Jun Guo, John Blenis

{"title":"Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism","authors":"Zhongchi Li, Shuchen Liu, Wenbing Jin, Leyi Xiao, Olivia Kester, Nayah Bullen, Xuanrong Chen, Un In Chan, Jude Owiredu, Zhucui Li, Rabia Khan, Jennifer Endress, Moniquetta Shafer, Vivien Low, Nikolaos Koundouros, Sungyun Cho, Christopher Barbieri, Chun-Jun Guo, John Blenis","doi":"10.1038/s42255-026-01583-z","DOIUrl":"10.1038/s42255-026-01583-z","url":null,"abstract":"Enhanced cholesterol synthesis and lipid droplet accumulation are hallmarks of aggressive prostate cancer, yet how tumour cells sense metabolic inputs to dynamically regulate cholesterol homeostasis remains poorly defined. Here we uncover a metabolic signalling mechanism in which prostate cancer cells remodel propionyl-CoA metabolism to support stress adaptation during disease progression. We show that the catabolism of branched-chain amino acid, specifically isoleucine and valine, is the primary source of intracellular propionyl-CoA in prostate cancer cells. Beyond its metabolic role, propionyl-CoA functions as a signalling molecule that stabilizes nuclear sterol regulatory element-binding protein 2 (SREBP2) through site-specific lysine propionylation, thereby enhancing its transcriptional activity. This activation promotes cholesterol biosynthesis, fuels de novo androgen production, and sustains androgen receptor signalling under metabolic and therapeutic stress, including androgen deprivation. Together, our findings establish propionyl-CoA as a key metabolic signal linking amino acid catabolism to cholesterol-driven oncogenic programmes and highlight targeting isoleucine and valine metabolism as a potential strategy to disrupt lipid reprogramming in prostate cancer. Rewiring of branched-chain amino acid catabolism in prostate cancer fuels propionyl-CoA synthesis, lysine propionylation and stabilization of SREBP2, leading to increased cholesterol and androgen synthesis, and thus promotes metabolic adaptation of cancer cells and disease progression.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 8","pages":"1772-1790"},"PeriodicalIF":27.5,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-026-01583-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148769293","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}

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The hallmarks of skeletal muscle health 骨骼肌健康的标志。

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-08-20 DOI: 10.1038/s42255-026-01595-9

Anna Vainshtein, Bert Blaauw, Katrien De Bock, Pura Munoz-Canoves, Eric N. Olson, Coen A. C. Ottenheijm, Erik A. Richter, Jorge L. Ruas, Laurent Schaffer, Bruce Spiegelman, Marco Sandri

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Intestinal cGAS–STING–IFN signalling promotes obesity by downregulating microbiota-derived IAA in male mice 肠道cGAS-STING-IFN信号通过下调微生物来源的IAA促进雄性小鼠肥胖

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-08-19 DOI: 10.1038/s42255-026-01562-4

Jiangming Deng, Wen Meng, Yuanqin Yang, Ting Xiao, Zhangliu Jin, Jing Wang, Qing-xin Li, Lingxiang Xie, Jingyi Hu, Rong Song, Yibo Hu, Yi Chu, Qing Li, Ping Jin, Zheng Wang, Irene XY Wu, Feng Liu, Yang Xiao

{"title":"Intestinal cGAS–STING–IFN signalling promotes obesity by downregulating microbiota-derived IAA in male mice","authors":"Jiangming Deng, Wen Meng, Yuanqin Yang, Ting Xiao, Zhangliu Jin, Jing Wang, Qing-xin Li, Lingxiang Xie, Jingyi Hu, Rong Song, Yibo Hu, Yi Chu, Qing Li, Ping Jin, Zheng Wang, Irene XY Wu, Feng Liu, Yang Xiao","doi":"10.1038/s42255-026-01562-4","DOIUrl":"10.1038/s42255-026-01562-4","url":null,"abstract":"The gut constantly interacts with both pathogens and dietary signals, but how it balances immune and metabolic responses remains unclear. Here we show that intestinal cGAS, a key DNA sensor, acts as a regulator linking gut immunity to whole-body metabolism. We show that cGAS signalling is activated in the intestines of humans and male mice with obesity, leading to increased type I interferon production and heightened immune activity in intestinal cells. Strikingly, deleting cGAS specifically in intestinal epithelial cells enhances energy expenditure, protects against diet-induced obesity and improves metabolic health. These effects depend on the gut microbiota, particularly Lactobacillus murinus and its metabolite indole-3-acetic acid (IAA), which promotes adipose thermogenesis. Our findings position intestinal cGAS as a key driver of obesity through gut-to-fat signalling and suggest that targeting the intestinal cGAS–microbiota IAA axis could offer promising strategies to combat obesity and related metabolic diseases. cGAS–STING signalling in intestinal epithelial cells modulates gut microbiome-derived indole-3-acetic acid production to regulate adipose thermogenesis and systemic metabolic health.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 8","pages":"1713-1729"},"PeriodicalIF":27.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148769313","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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Author Correction: Maternal exercise prevents metabolic disorders in offspring mice through SERPINA3C 作者更正：母体运动通过SERPINA3C预防子代小鼠代谢紊乱。

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-08-16 DOI: 10.1038/s42255-026-01609-6

Yang Li, Ruo-Ying Li, Jie-Ying Zhu, Min Chen, Wang-Jing Mu, Hong-Yang Luo, Shan Li, Lin-Jing Yan, Meng-Ting Yin, Xin Li, Hu-Min Chen, Liang Guo

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Parabrachial neurons orchestrate cold-induced homeostatic responses 臂旁神经元协调冷诱导的稳态反应

IF 27.5 1区医学

Nature metabolism Pub Date : 2026-08-13 DOI: 10.1038/s42255-026-01565-1

Sieun Jung, Anna Kondaurova, Myungsun Lee, JiSoo Jennifer Kwon, Hyeyoung Shin, Sung-Yon Kim

{"title":"Parabrachial neurons orchestrate cold-induced homeostatic responses","authors":"Sieun Jung, Anna Kondaurova, Myungsun Lee, JiSoo Jennifer Kwon, Hyeyoung Shin, Sung-Yon Kim","doi":"10.1038/s42255-026-01565-1","DOIUrl":"10.1038/s42255-026-01565-1","url":null,"abstract":"Thermoregulation is a fundamental physiological process essential for survival1,2, yet how the brain represents peripheral cold sensory information and coordinates diverse adaptive responses remains incompletely understood3. Here we identify cold-activated neurons in the parabrachial nucleus (hereafter, PBCold neurons) as primary recipients of cold sensory input in the brain, using activity-dependent genetic labelling in mice4,5. PBCold neurons exhibit rapid and sustained activation across a wide range of cold stimuli, indicating persistent encoding of environmental cooling. Transient or permanent silencing of these neurons disrupts cold-induced adaptations spanning multiple domains, including autonomic (brown adipose tissue thermogenesis and tail vasoconstriction), somatic (skeletal muscle shivering), behavioural (cold avoidance), metabolic (cold-induced hyperphagia) and affective (dopamine release to rewarding cool stimuli) responses, and compromises survival under severe cold. Conversely, activating PBCold neurons promotes warmth-seeking behaviour and increases food intake and energy expenditure. Molecular profiling identifies Grp and Trhr as highly specific yet partially efficient markers for PBCold neuron subsets. Together, these findings establish PBCold neurons as a critical hub coordinating cold-responsive adaptations, advancing our understanding of the central mechanisms governing thermal homeostasis. Using activity-dependent genetic labelling in mice, the authors identify cold-activated neurons in the parabrachial nucleus that coordinate autonomic, metabolic, behavioural and affective adaptations to cold exposure.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 8","pages":"1679-1693"},"PeriodicalIF":27.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148728926","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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