Nature metabolism最新文献

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Career pathways, part 19. 职业道路，第19部分。

IF 20.8 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism

Pub Date : 2026-02-12 DOI: 10.1038/s42255-026-01470-7

Xiaofei Yu, Michael Lukey

引用次数: 0

Fuelling the brain with calcium. 为大脑补充钙。

IF 20.8 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism

Pub Date : 2026-02-11 DOI: 10.1038/s42255-025-01448-x

Adrian Marti Pastor, Yi-Heng Tai, Thomas Misgeld

引用次数: 0

Mitochondrial Ca2+ efflux controls neuronal metabolism and long-term memory across species 线粒体Ca2+外排控制跨物种的神经元代谢和长期记忆

IF 20.8 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism

Pub Date : 2026-02-11 DOI: 10.1038/s42255-026-01451-w

Anjali Amrapali Vishwanath, Typhaine Comyn, Rodrigo G. Mira, Claire Brossier, Carlos Pascual-Caro, Maya Faour, Kahina Boumendil, Chaitanya Chintaluri, Carla Ramon-Duaso, Ruolin Fan, Kishalay Ghosh, Helen Farrants, Jean-Paul Berwick, Riya Sivakumar, Mario Lopez-Manzaneda, Eric R. Schreiter, Thomas Preat, Tim P. Vogels, Vidhya Rangaraju, Arnau Busquets-Garcia, Pierre-Yves Plaçais, Alice Pavlowsky, Jaime de Juan-Sanz

From insects to mammals, essential brain functions, such as forming long-term memories (LTMs), increase metabolic activity in stimulated neurons to meet the energetic demand associated with brain activation. However, while impairing neuronal metabolism limits brain performance, whether expanding the metabolic capacity of neurons boosts brain function remains poorly understood. Here, we show that LTM formation of flies and mice can be enhanced by increasing mitochondrial metabolism in central memory circuits. By knocking down the mitochondrial Ca2+ exporter Letm1, we favour Ca2+ retention in the mitochondrial matrix of neurons due to reduction of mitochondrial H+/Ca2+ exchange. The resulting increase in mitochondrial Ca2+ over-activates mitochondrial metabolism in neurons of central memory circuits, leading to improved LTM storage in training paradigms in which wild-type counterparts of both species fail to remember. Our findings unveil an evolutionarily conserved mechanism that controls mitochondrial metabolism in neurons and indicate its involvement in shaping higher brain functions, such as LTM.

从昆虫到哺乳动物，基本的大脑功能，如形成长期记忆（ltm），增加受刺激神经元的代谢活动，以满足与大脑激活相关的能量需求。然而，虽然损害神经元代谢限制了大脑的表现，但扩大神经元的代谢能力是否能促进大脑功能，人们仍然知之甚少。在这里，我们表明，通过增加中央记忆回路中的线粒体代谢，可以增强果蝇和小鼠的LTM形成。通过敲除线粒体Ca2+出口者Letm1，由于线粒体H+/Ca2+交换减少，我们有利于神经元线粒体基质中的Ca2+保留。由此产生的线粒体Ca2+的增加过度激活了中央记忆回路神经元中的线粒体代谢，导致训练范式中LTM存储的改善，而这两个物种的野生型对应体都无法记忆。我们的发现揭示了一种控制神经元线粒体代谢的进化保守机制，并表明其参与塑造高级脑功能，如LTM。

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引用次数: 0

SLC6A6 imports taurine into mitochondria to sustain mitochondrial translation and tumour growth. SLC6A6将牛磺酸输入线粒体以维持线粒体翻译和肿瘤生长。

IF 20.8 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism

Pub Date : 2026-02-06 DOI: 10.1038/s42255-026-01455-6

Liucheng Li, Jianwei You, Zi-Qing Chai, Xueshan Li, Xinlei Cai, Lin Wang, Fang Yang, Lingzhi Zhu, Wen Mi, Xinyi Xia, Haohang Yan, Fei Li, Juan Wang, Tong-Jin Zhao, Ligong Chen, Hongbin Ji, Pingyu Liu, Xiao-Long Zhou, Li Chen, Fuming Li

Taurine plays a crucial role in mitochondrial translation. Mammalian cells obtain taurine via exogenous uptake mediated by the plasma membrane transporter SLC6A6 or via cytosolic biosynthesis. However, it remains unclear how taurine enters mitochondria and impacts cellular metabolism. Here we show that SLC6A6, but not exogenous taurine, is essential for mitochondrial metabolism and cancer cell growth. We discover that SLC6A6 also localizes to mitochondria and imports taurine for mitochondrial transfer RNA modifications. SLC6A6 deficiency specifically reduces mitochondrial taurine abundance and abrogates mitochondrial translation and cell proliferation. We identify protein kinase A as a regulator of SLC6A6 subcellular localization, as it promotes SLC6A6 presence at the plasma membrane while inhibiting its mitochondrial localization. Furthermore, we identify NFAT5 as a key regulator of mitochondrial function through SLC6A6 and demonstrate that targeting the NFAT5-SLC6A6 axis markedly impairs mitochondrial translation and tumour growth. Together, these findings suggest that SLC6A6 is a mitochondrial taurine transporter and an exploitable metabolic dependency in cancer.

牛磺酸在线粒体翻译中起着关键作用。哺乳动物细胞通过质膜转运蛋白SLC6A6介导的外源性摄取或细胞质生物合成获得牛磺酸。然而，牛磺酸如何进入线粒体并影响细胞代谢尚不清楚。我们发现SLC6A6，而不是外源性牛磺酸，是线粒体代谢和癌细胞生长所必需的。我们发现SLC6A6也定位于线粒体并输入牛磺酸进行线粒体转移RNA修饰。SLC6A6缺乏特异性地降低线粒体牛磺酸丰度，并取消线粒体翻译和细胞增殖。我们发现蛋白激酶A是SLC6A6亚细胞定位的调节因子，因为它促进SLC6A6在质膜上的存在，同时抑制其线粒体定位。此外，我们通过SLC6A6确定NFAT5是线粒体功能的关键调节因子，并证明靶向NFAT5-SLC6A6轴显著损害线粒体翻译和肿瘤生长。总之，这些发现表明SLC6A6是线粒体牛磺酸转运蛋白，是癌症中可利用的代谢依赖。

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引用次数: 0

Mitochondrial SLC6A6 supports taurine transport. 线粒体SLC6A6支持牛磺酸运输。

IF 20.8 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism

Pub Date : 2026-02-06 DOI: 10.1038/s42255-026-01471-6

Katsuhisa Inoue

引用次数: 0

Feeding-regulated glycogen metabolism drives rhythmic liver protein secretion. 摄食调节的糖原代谢驱动有节奏的肝蛋白分泌。

IF 20.8 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism

Pub Date : 2026-02-05 DOI: 10.1038/s42255-026-01453-8

Meltem Weger, Daniel Mauvoisin, Dominic Hoyle, Jingkui Wang, Eva Martin, James Rae, Charles Ferguson, Glynis Klinke, Michelle Cielesh, Kyle L Macauslane, Mark Larance, Manfredo Quadroni, Iain Templeman, Jean-Philippe Walhin, Leonidas G Karagounis, James A Betts, Jonathan D Johnston, Fanny Durussel, Dmitri Firsov, Stephane Fournier, Olivier Müller, Benjamin L Schulz, Robert G Parton, Benjamin D Weger, Frédéric Gachon

The liver has a key role in inter-organ communication by secreting most circulating plasma proteins. However, the mechanisms governing hepatic protein secretion remain unclear. Here we show that hepatic protein secretion follows a diurnal rhythm regulated by food intake in humans and mice. Using liver microsomal proteomics, we find that proteins implicated in the early secretory pathway, such as protein glycosylation and folding in the endoplasmic reticulum (ER) and Golgi apparatus, exhibit a rhythmic expression profile, which is abolished in Bmal1-knockout mice. Mechanistically, we show that hepatic glycogenolysis provides substrates for protein N-glycosylation. In mice, perturbing hepatic glycogenolysis with pharmacological or nutritional interventions leads to ER stress and attenuates diurnal protein secretion. We confirm these results in humans, as genetic variants associated with glycogen storage disease and congenital disorders of glycosylation also alter hepatic protein secretion. Overall, our work uncovers hepatic glycogen metabolism as a circadian regulator of protein secretion.

肝脏通过分泌大多数循环血浆蛋白在器官间通讯中起关键作用。然而，控制肝脏蛋白分泌的机制仍不清楚。在这里，我们表明肝脏蛋白质分泌遵循由人类和小鼠的食物摄入调节的昼夜节律。利用肝微粒体蛋白质组学，我们发现与早期分泌途径有关的蛋白质，如内质网（ER）和高尔基体中的蛋白质糖基化和折叠，表现出有节奏的表达谱，在bmal1基因敲除小鼠中被消除。从机制上讲，我们发现肝糖原分解为蛋白质n -糖基化提供了底物。在小鼠中，通过药物或营养干预干扰肝糖原溶解可导致内质网应激并减弱昼夜蛋白分泌。我们在人类中证实了这些结果，因为与糖原储存病和先天性糖基化疾病相关的遗传变异也会改变肝脏蛋白分泌。总的来说，我们的工作揭示了肝糖原代谢作为蛋白质分泌的昼夜调节因子。

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引用次数: 0

Mitochondrial superoxide regulates nuclear envelope integrity and ageing via redox-mediated lipid metabolism 线粒体超氧化物通过氧化还原介导的脂质代谢调节核膜完整性和衰老

IF 20.8 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism

Pub Date : 2026-02-03 DOI: 10.1038/s42255-026-01452-9

Peng X. Chen, Leyuan Zhang, Xueying Wu, Zhiqiang Liang, Xusheng Hao, Qingyuan Zhu, Ying Liu, Jinrou Zheng, Qian Zhang, Qinmeng Yang, Fan Zhou, Chunbao Zhou, Ye Tian

The nuclear envelope (NE) is essential for cellular homeostasis, yet its integrity declines with age, accelerating functional deterioration. Here we report a mitochondria-to-NE signalling pathway that safeguards NE integrity through redox-dependent lipid metabolism. In Caenorhabditis elegans, reducing mitochondrial ETC activity preserves NE morphology during ageing. This effect requires developmental mitochondrial superoxide, which downregulates SBP-1 (SREBP orthologue) and suppresses unsaturated fatty acid biosynthesis. The resulting reduction in unsaturated fatty acid levels limits lipid peroxidation, thereby preserving NE structure. Interventions targeting lipid peroxidation preserve NE integrity, extend lifespan in worms and ameliorate senescence-associated phenotypes in human fibroblasts and monkey cells mimicking Hutchinson–Gilford progeria syndrome disease. Our findings reveal a previously unrecognized role for mitochondrial superoxide as a protective developmental signal that programs long-term NE integrity. This work establishes lipid peroxidation control as a conserved strategy to delay nuclear ageing and highlights redox–lipid cross-talk as a therapeutic axis for healthy ageing.

核膜（NE）对细胞稳态至关重要，但其完整性随着年龄的增长而下降，加速了功能的恶化。在这里，我们报告了线粒体到NE的信号通路，通过氧化还原依赖的脂质代谢来保护NE的完整性。在秀丽隐杆线虫中，减少线粒体ETC活性可以在衰老过程中保持NE形态。这种作用需要发育线粒体超氧化物，其下调SBP-1 （SREBP同源物）并抑制不饱和脂肪酸的生物合成。由此产生的不饱和脂肪酸水平的降低限制了脂质过氧化，从而保留了NE结构。针对脂质过氧化的干预措施可以保持NE的完整性，延长蠕虫的寿命，改善人类成纤维细胞和猴子细胞模仿Hutchinson-Gilford早衰综合征疾病的衰老相关表型。我们的研究结果揭示了线粒体超氧化物作为一种保护性发育信号的作用，该信号可编程长期NE完整性。本研究确立了脂质过氧化控制作为延缓核衰老的保守策略，并强调氧化还原-脂质串导是健康衰老的治疗轴。

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引用次数: 0

Mitochondrial superoxide signals shield the nucleus to delay ageing. 线粒体超氧化物信号保护细胞核延缓衰老。

IF 20.8 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism

Pub Date : 2026-02-03 DOI: 10.1038/s42255-026-01461-8

引用次数: 0

Glucose deprivation drives LIF-dependent lung cancer. 葡萄糖剥夺驱动liff依赖性肺癌。

IF 20.8 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism

Pub Date : 2026-01-30 DOI: 10.1038/s42255-025-01437-0

Fedra Luciano-Mateo,Joaquim Moreno-Caceres,Miguel Hernández-Madrigal,Franziska Püschel,Lidia Collado-Rodriguez,Francesca Favaro,Sara Hijazo-Pechero,Mabel Cruz-Rodríguez,Felipe Jiménez-Hernández,Verónica Villagrasa-Araya,Nil Figueras-Duch,Jaime Redondo-Pedraza,Didac Palau-Gallinat,Silvia Plans-Marin,Agnés Figueras,Pedro Fuentes Varela,Lidia de Benito-Gómez,Antonio Gentilella,José Carlos Perales,Xavier Solé,Andrés Méndez-Lucas,Francesc Viñals,Ernest Nadal,Cristina Muñoz-Pinedo

Glucose deficiency promotes the secretion of cytokines and inflammatory factors to rewire the immune compartment and restore blood flow. Here we show that cancer cells subjected to glucose deprivation or hypoxia, but not to other metabolic stressors, secrete LIF, an interleukin-6 family cytokine implicated in the development of solid tumours. We find that mannose supplementation prevents LIF release by sustaining multiple metabolic pathways in the absence of glucose. Mechanistically, LIF release is associated with impairment of N-glycosylation and activation of PERK and MEK MAP kinases. In mouse models of non-small-cell lung cancer, reduction of LIF impairs angiogenesis and tumour growth, rewires the immune system toward an antitumour phenotype and inhibits tumour implantation in the lung. In individuals with non-small-cell lung cancer, LIF levels correlate with markers of hypoxia, glucose deprivation and angiogenesis. Overall, these findings identify LIF as a metabolic stress-induced cytokine that could be targeted to disrupt adaptive responses in cancer.

葡萄糖缺乏促进细胞因子和炎症因子的分泌，以重新连接免疫室并恢复血液流动。在这里，我们发现癌细胞受到葡萄糖剥夺或缺氧，而不是其他代谢应激源，分泌LIF，一种与实体肿瘤发展有关的白细胞介素-6家族细胞因子。我们发现补充甘露糖可以在缺乏葡萄糖的情况下通过维持多种代谢途径来阻止LIF的释放。从机制上讲，LIF释放与n -糖基化损伤以及PERK和MEK MAP激酶的激活有关。在非小细胞肺癌小鼠模型中，LIF的减少会损害血管生成和肿瘤生长，使免疫系统向抗肿瘤表型转变，并抑制肿瘤在肺中的植入。在非小细胞肺癌患者中，LIF水平与缺氧、葡萄糖剥夺和血管生成标志物相关。总的来说，这些发现确定了LIF是一种代谢应激诱导的细胞因子，可以靶向破坏癌症的适应性反应。

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引用次数: 0

Adversity, adiposity, nutrition and metabolic well-being in multi-ethnic Asia 亚洲多民族的逆境、肥胖、营养与代谢健康

IF 20.8 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism

Pub Date : 2026-01-29 DOI: 10.1038/s42255-025-01441-4

Theresia H. Mina, Pritesh R. Jain, Nita G. Forouhi, John C. Chambers

Obesity, diabetes and cardiovascular disease are rising rapidly in Asia. Population-based data consistently show that Asians are at higher risk for these non-communicable diseases than their European counterparts, especially when living in urban and migrant settings. Contrary to initial hypotheses, genetic susceptibility factors only partially explain globally divergent health outcomes. In this Perspective, we discuss potential additional mechanisms to explain this divergence. We review the global disparities in the cardiometabolic disease burden and the role of genetic variation. We then summarize potential pathways linking prenatal and postnatal adversity with unfavourable nutrition, increased adiposity and altered metabolic well-being in Asian populations. In parallel, molecular epidemiological studies are providing insights into how life-course exposures and environmental adversity intersect with adverse nutrition to establish the functional genomic changes that may drive cardiometabolic risk in global Asian populations. We highlight opportunities in precision health studies to advance Asian health through the identification of underlying aetiology critical to the development of effective interventions to promote and maintain metabolic health in current and future generations of Asian individuals worldwide. In this Perspective, the authors discuss reasons for the increased cardiometabolic disease risk observed in Asian populations, including nutrition, genetic factors and environmental adversity.

肥胖症、糖尿病和心血管疾病在亚洲正在迅速增加。基于人口的数据一致表明，亚洲人患这些非传染性疾病的风险高于欧洲人，尤其是生活在城市和移民环境中的亚洲人。与最初的假设相反，遗传易感性因素只能部分解释全球不同的健康结果。在这个观点中，我们讨论了解释这种差异的潜在附加机制。我们回顾了心脏代谢疾病负担的全球差异和遗传变异的作用。然后，我们总结了亚洲人群中产前和产后逆境与营养不良、肥胖增加和代谢健康改变之间的潜在途径。与此同时，分子流行病学研究提供了关于生命过程暴露和环境逆境如何与不良营养交叉的见解，以建立可能驱动全球亚洲人群心脏代谢风险的功能基因组变化。我们强调精确健康研究的机会，通过确定潜在的病因来促进亚洲人的健康，这对于开发有效的干预措施来促进和维持当今和未来亚洲人的代谢健康至关重要。在这一观点中，作者讨论了在亚洲人群中观察到的心脏代谢疾病风险增加的原因，包括营养、遗传因素和环境逆境。

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