Nature metabolism最新文献_第10页

The time is now: accounting for time-of-day effects to improve reproducibility and translation of metabolism research 时间就是现在：考虑一天中的时间效应，以提高代谢研究的可重复性和转译性

IF 18.9 1区医学

Nature metabolism Pub Date : 2025-03-17 DOI: 10.1038/s42255-025-01237-6

Shaunak Deota, Julie S. Pendergast, Ullas Kolthur-Seetharam, Karyn A. Esser, Frédéric Gachon, Gad Asher, Charna Dibner, Salvador Aznar Benitah, Carolina Escobar, Deborah M. Muoio, Eric Erquan Zhang, Gökhan S. Hotamışlıgil, Joseph Bass, Joseph S. Takahashi, Joshua D. Rabinowitz, Katja A. Lamia, Rafael de Cabo, Shingo Kajimura, Valter D. Longo, Ying Xu, Mitchell A. Lazar, Eric Verdin, Juleen R. Zierath, Johan Auwerx, Daniel J. Drucker, Satchidananda Panda

{"title":"The time is now: accounting for time-of-day effects to improve reproducibility and translation of metabolism research","authors":"Shaunak Deota, Julie S. Pendergast, Ullas Kolthur-Seetharam, Karyn A. Esser, Frédéric Gachon, Gad Asher, Charna Dibner, Salvador Aznar Benitah, Carolina Escobar, Deborah M. Muoio, Eric Erquan Zhang, Gökhan S. Hotamışlıgil, Joseph Bass, Joseph S. Takahashi, Joshua D. Rabinowitz, Katja A. Lamia, Rafael de Cabo, Shingo Kajimura, Valter D. Longo, Ying Xu, Mitchell A. Lazar, Eric Verdin, Juleen R. Zierath, Johan Auwerx, Daniel J. Drucker, Satchidananda Panda","doi":"10.1038/s42255-025-01237-6","DOIUrl":"10.1038/s42255-025-01237-6","url":null,"abstract":"The constant expansion of the field of metabolic research has led to more nuanced and sophisticated understanding of the complex mechanisms that underlie metabolic functions and diseases. Collaborations with scientists of various fields such as neuroscience, immunology and drug discovery have further enhanced the ability to probe the role of metabolism in physiological processes. However, many behaviours, endocrine and biochemical processes, and the expression of genes, proteins and metabolites have daily ~24-h biological rhythms and thus peak only at specific times of the day. This daily variation can lead to incorrect interpretations, lack of reproducibility across laboratories and challenges in translating preclinical studies to humans. In this Review, we discuss the biological, environmental and experimental factors affecting circadian rhythms in rodents, which can in turn alter their metabolic pathways and the outcomes of experiments. We recommend that these variables be duly considered and suggest best practices for designing, analysing and reporting metabolic experiments in a circadian context. This broad group of authors summarizes the impact of circadian factors on metabolic biology and offers recommendations on how to account for and report biological, environmental and experimental factors affecting circadian rhythms in metabolic studies in rodents.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 3","pages":"454-468"},"PeriodicalIF":18.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42255-025-01237-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635690","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

SIRT5 slows skeletal muscle ageing by alleviating inflammation SIRT5通过减轻炎症来减缓骨骼肌老化

IF 18.9 1区医学

Nature metabolism Pub Date : 2025-03-14 DOI: 10.1038/s42255-025-01228-7

Vera Gorbunova, Andrei Seluanov

引用次数: 0

SIRT5 safeguards against primate skeletal muscle ageing via desuccinylation of TBK1 SIRT5通过TBK1去琥珀酰化防止灵长类骨骼肌老化

IF 18.9 1区医学

Nature metabolism Pub Date : 2025-03-14 DOI: 10.1038/s42255-025-01235-8

Qian Zhao, Ying Jing, Xiaoyu Jiang, Xin Zhang, Feifei Liu, Haoyan Huang, Zhihua Zhang, Haijun Wang, Shuhui Sun, Shuai Ma, Weiqi Zhang, Yang Yu, Xiaobing Fu, Guoguang Zhao, Jing Qu, Si Wang, Guang-Hui Liu

{"title":"SIRT5 safeguards against primate skeletal muscle ageing via desuccinylation of TBK1","authors":"Qian Zhao, Ying Jing, Xiaoyu Jiang, Xin Zhang, Feifei Liu, Haoyan Huang, Zhihua Zhang, Haijun Wang, Shuhui Sun, Shuai Ma, Weiqi Zhang, Yang Yu, Xiaobing Fu, Guoguang Zhao, Jing Qu, Si Wang, Guang-Hui Liu","doi":"10.1038/s42255-025-01235-8","DOIUrl":"10.1038/s42255-025-01235-8","url":null,"abstract":"Ageing-induced skeletal muscle deterioration contributes to sarcopenia and frailty, adversely impacting the quality of life in the elderly. However, the molecular mechanisms behind primate skeletal muscle ageing remain largely unexplored. Here, we show that SIRT5 expression is reduced in aged primate skeletal muscles from both genders. SIRT5 deficiency in human myotubes hastens cellular senescence and intensifies inflammation. Mechanistically, we demonstrate that TBK1 is a natural substrate for SIRT5. SIRT5 desuccinylates TBK1 at lysine 137, which leads to TBK1 dephosphorylation and the suppression of the downstream inflammatory pathway. Using SIRT5 lentiviral vectors for skeletal muscle gene therapy in male mice enhances physical performance and alleviates age-related muscle dysfunction. This study sheds light on the molecular underpinnings of skeletal muscle ageing and presents the SIRT5–TBK1 pathway as a promising target for combating age-related skeletal muscle degeneration. SIRT5 protects against primate skeletal muscle ageing through TBK1 desuccinylation, which inhibits the downstream inflammatory and senescent phenotypes.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 3","pages":"556-573"},"PeriodicalIF":18.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618500","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 cyclic metabolic switching theory of intermittent fasting 间歇性禁食的循环代谢转换理论

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-03-14 DOI: 10.1038/s42255-025-01254-5

Mark P. Mattson

引用次数: 0

Human gut microbial aromatic amino acid and related metabolites prevent obesity through intestinal immune control 人体肠道微生物芳香族氨基酸及其代谢物通过肠道免疫控制预防肥胖

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-03-14 DOI: 10.1038/s42255-025-01246-5

Zengliang Jiang, Liuqing He, Diyin Li, Laibao Zhuo, Lingjun Chen, Rui-Qi Shi, Jianhua Luo, Yuhui Feng, Yuhui Liang, Danyang Li, Xiao Congmei, Yuanqing Fu, Yu-ming Chen, Ju-Sheng Zheng, Liang Tao

引用次数: 0

More protein in ultra-processed foods: no shortcut to eating less 超加工食品中含有更多蛋白质：少吃没有捷径

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-03-13 DOI: 10.1038/s42255-025-01258-1

Rikard Landberg, Therese Karlsson

引用次数: 0

Short-term effects of high-protein, lower-carbohydrate ultra-processed foods on human energy balance 高蛋白、低碳水化合物超加工食品对人体能量平衡的短期影响

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-03-13 DOI: 10.1038/s42255-025-01247-4

Franziska A. Hägele, Catrin Herpich, Jana Koop, Jonas Grübbel, Rebecca Dörner, Svenja Fedde, Oliver Götze, Yves Boirie, Manfred J. Müller, Kristina Norman, Anja Bosy-Westphal

{"title":"Short-term effects of high-protein, lower-carbohydrate ultra-processed foods on human energy balance","authors":"Franziska A. Hägele, Catrin Herpich, Jana Koop, Jonas Grübbel, Rebecca Dörner, Svenja Fedde, Oliver Götze, Yves Boirie, Manfred J. Müller, Kristina Norman, Anja Bosy-Westphal","doi":"10.1038/s42255-025-01247-4","DOIUrl":"https://doi.org/10.1038/s42255-025-01247-4","url":null,"abstract":"Protein-enriched ultra-processed foods (UPFs) are generally perceived as a healthy and favourable dietary choice for weight management. However, compared with low-processed foods, the consumption of UPFs has been demonstrated to result in overfeeding and gains in body weight and fat mass. Here we investigate the short-term effects of protein-enriched UPFs on energy intake and energy balance in a single-blind crossover trial involving 21 healthy young adults, who were randomly assigned to 2 UPF diets for 54 hours in a whole-room calorimeter. Participants received either a high-protein (30%) and lower-carbohydrate (29%) diet (HPLC-UPF) or a normal-protein (13%) and normal-carbohydrate (46%) diet (NPNC-UPF). Meals were equally palatable, matched for calories, fat and fibre, and consumed ad libitum. As primary outcomes, compared with NPNC-UPF consumption, the HPLC-UPF diet resulted in a higher energy expenditure (128 ± 98 kcal d−1) and lower energy intake (−196 ± 396 kcal d−1), leading to a less-positive energy balance (18% versus 32%) with gains in protein and carbohydrate balance only. Postprandial ghrelin levels were lower, whereas glucagon and peptide YY levels were higher with HPLC-UPF compared with NPNC-UPF (secondary outcomes). Despite a reduction in energy intake and increased energy expenditure, the short-term consumption of protein-enriched UPFs did not prevent overeating but did favourably affect energy partitioning. ClinicalTrials.gov registration: NCT05337007.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"14 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607962","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

Glycogen drives tumour initiation and progression in lung adenocarcinoma 糖原驱动肺腺癌肿瘤的发生和发展

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-03-11 DOI: 10.1038/s42255-025-01243-8

Harrison A. Clarke, Tara R. Hawkinson, Cameron J. Shedlock, Terrymar Medina, Roberto A. Ribas, Lei Wu, Zizhen Liu, Xin Ma, Yi Xia, Yu Huang, Xing He, Josephine E. Chang, Lyndsay E. A. Young, Jelena A. Juras, Michael D. Buoncristiani, Alexis N. James, Anna Rushin, Matthew E. Merritt, Annette Mestas, Jessica F. Lamb, Elena C. Manauis, Grant L. Austin, Li Chen, Pankaj K. Singh, Jiang Bian, Craig W. Vander Kooi, B. Mark Evers, Christine F. Brainson, Derek B. Allison, Matthew S. Gentry, Ramon C. Sun

{"title":"Glycogen drives tumour initiation and progression in lung adenocarcinoma","authors":"Harrison A. Clarke, Tara R. Hawkinson, Cameron J. Shedlock, Terrymar Medina, Roberto A. Ribas, Lei Wu, Zizhen Liu, Xin Ma, Yi Xia, Yu Huang, Xing He, Josephine E. Chang, Lyndsay E. A. Young, Jelena A. Juras, Michael D. Buoncristiani, Alexis N. James, Anna Rushin, Matthew E. Merritt, Annette Mestas, Jessica F. Lamb, Elena C. Manauis, Grant L. Austin, Li Chen, Pankaj K. Singh, Jiang Bian, Craig W. Vander Kooi, B. Mark Evers, Christine F. Brainson, Derek B. Allison, Matthew S. Gentry, Ramon C. Sun","doi":"10.1038/s42255-025-01243-8","DOIUrl":"https://doi.org/10.1038/s42255-025-01243-8","url":null,"abstract":"Lung adenocarcinoma (LUAD) is an aggressive cancer defined by oncogenic drivers and metabolic reprogramming. Here we leverage next-generation spatial screens to identify glycogen as a critical and previously underexplored oncogenic metabolite. High-throughput spatial analysis of human LUAD samples revealed that glycogen accumulation correlates with increased tumour grade and poor survival. Furthermore, we assessed the effect of increasing glycogen levels on LUAD via dietary intervention or via a genetic model. Approaches that increased glycogen levels provided compelling evidence that elevated glycogen substantially accelerates tumour progression, driving the formation of higher-grade tumours, while the genetic ablation of glycogen synthase effectively suppressed tumour growth. To further establish the connection between glycogen and cellular metabolism, we developed a multiplexed spatial technique to simultaneously assess glycogen and cellular metabolites, uncovering a direct relationship between glycogen levels and elevated central carbon metabolites essential for tumour growth. Our findings support the conclusion that glycogen accumulation drives LUAD cancer progression and provide a framework for integrating spatial metabolomics with translational models to uncover metabolic drivers of cancer.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"13 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589835","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

Disrupting cholesterol homeostasis in T cells boosts antitumour responses 破坏T细胞中的胆固醇稳态可以增强抗肿瘤反应

IF 18.9 1区医学

Nature metabolism Pub Date : 2025-03-10 DOI: 10.1038/s42255-025-01240-x

Kelly T. Kennewick, Steven J. Bensinger

引用次数: 0

A functional single-cell metabolic survey identifies Elovl1 as a target to enhance CD8+ T cell fitness in solid tumours 一项功能性单细胞代谢调查发现，Elovl1是实体肿瘤中增强CD8+ T细胞适应度的靶标

IF 18.9 1区医学

Nature metabolism Pub Date : 2025-03-10 DOI: 10.1038/s42255-025-01233-w

Samantha Pretto, Qian Yu, Pierre Bourdely, Sarah Trusso Cafarello, Heleen H. Van Acker, Joren Verelst, Elena Richiardone, Lotte Vanheer, Amir Roshanzadeh, Franziska Schneppenheim, Charlotte Cresens, Maria Livia Sassano, Jonas Dehairs, Martin Carion, Shehab Ismail, Patrizia Agostinis, Susana Rocha, Tobias Bald, Johan Swinnen, Cyril Corbet, Sophia Y. Lunt, Bernard Thienpont, Mario Di Matteo, Massimiliano Mazzone

{"title":"A functional single-cell metabolic survey identifies Elovl1 as a target to enhance CD8+ T cell fitness in solid tumours","authors":"Samantha Pretto, Qian Yu, Pierre Bourdely, Sarah Trusso Cafarello, Heleen H. Van Acker, Joren Verelst, Elena Richiardone, Lotte Vanheer, Amir Roshanzadeh, Franziska Schneppenheim, Charlotte Cresens, Maria Livia Sassano, Jonas Dehairs, Martin Carion, Shehab Ismail, Patrizia Agostinis, Susana Rocha, Tobias Bald, Johan Swinnen, Cyril Corbet, Sophia Y. Lunt, Bernard Thienpont, Mario Di Matteo, Massimiliano Mazzone","doi":"10.1038/s42255-025-01233-w","DOIUrl":"10.1038/s42255-025-01233-w","url":null,"abstract":"Reprogramming T cell metabolism can improve intratumoural fitness. By performing a CRISPR/Cas9 metabolic survey in CD8+ T cells, we identified 83 targets and we applied single-cell RNA sequencing to disclose transcriptome changes associated with each metabolic perturbation in the context of pancreatic cancer. This revealed elongation of very long-chain fatty acids protein 1 (Elovl1) as a metabolic target to sustain effector functions and memory phenotypes in CD8+ T cells. Accordingly, Elovl1 inactivation in adoptively transferred T cells combined with anti-PD-1 showed therapeutic efficacy in resistant pancreatic and melanoma tumours. The accumulation of saturated long-chain fatty acids in Elovl1-deficient T cells destabilized INSIG1, leading to SREBP2 activation, increased plasma membrane cholesterol and stronger T cell receptor signalling. Elovl1-deficient T cells increased mitochondrial fitness and fatty acid oxidation, thus withstanding the metabolic stress imposed by the tumour microenvironment. Finally, ELOVL1 in CD8+ T cells correlated with anti-PD-1 response in patients with melanoma. Altogether, Elovl1 targeting synergizes with anti-PD-1 to promote effective T cell responses. Through a functional CRISPR/Cas9 screening, Pretto et al. identify Elovl1 as a target to improve antitumour immunity by remodelling T cell lipid metabolism.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 3","pages":"508-530"},"PeriodicalIF":18.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42255-025-01233-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582918","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