Cell metabolism最新文献_第3页

Remote limb ischemic conditioning alleviates steatohepatitis via extracellular vesicle-mediated muscle-liver crosstalk 远端肢体缺血调节通过细胞外囊泡介导的肌肝串扰减轻脂肪性肝炎

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-20 DOI: 10.1016/j.cmet.2025.02.009

Yichao Zhao, Ling Gao, Jianqing Chen, Jingze Wei, Guanqiao Lin, Kewei Hu, Wubin Zhao, Weijun Wei, Wei Huang, Lingchen Gao, Ancai Yuan, Kun Qian, Alex F. Chen, Jun Pu

{"title":"Remote limb ischemic conditioning alleviates steatohepatitis via extracellular vesicle-mediated muscle-liver crosstalk","authors":"Yichao Zhao, Ling Gao, Jianqing Chen, Jingze Wei, Guanqiao Lin, Kewei Hu, Wubin Zhao, Weijun Wei, Wei Huang, Lingchen Gao, Ancai Yuan, Kun Qian, Alex F. Chen, Jun Pu","doi":"10.1016/j.cmet.2025.02.009","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.02.009","url":null,"abstract":"Metabolic dysfunction-associated steatohepatitis (MASH) is an advanced form of liver disease with adverse outcomes. Manipulating interorgan communication is considered a promising strategy for managing metabolic disease, including steatohepatitis. Here, we report that remote limb ischemic conditioning (RIC), a clinically validated therapy for distant organ protection by transient muscle ischemia, significantly alleviated steatohepatitis in different mouse models. The beneficial effect of limb ischemic conditioning was mediated by muscle-to-liver transfer of small extracellular vesicles (sEVs) and their cargo microRNAs, leading to elevation of miR-181d-5p in the liver. Hepatic miR-181d-5p overexpression faithfully mirrored the molecular and histological benefits of limb ischemic conditioning by suppressing nuclear receptor 4A3 (NR4A3). Furthermore, circulating EVs from human volunteers undergoing limb ischemic conditioning improved steatohepatitis and transcriptomic perturbations in primary human hepatocytes and animal models. Our data underscore the translational potential of limb ischemic conditioning for steatohepatitis management and extend our understanding of muscle-liver crosstalk.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"56 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pyruvate metabolism enzyme DLAT promotes tumorigenesis by suppressing leucine catabolism 丙酮酸代谢酶DLAT通过抑制亮氨酸分解代谢促进肿瘤发生

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-19 DOI: 10.1016/j.cmet.2025.02.008

Ning Wang, Sijia Lu, Ziyi Cao, Huimin Li, Junting Xu, Qian Zhou, Hanrui Yin, Qiqi Qian, Xianjing Zhang, Mijia Tao, Quanxin Jiang, Peihui Zhou, Liaoyuan Zheng, Liu Han, Hongtao Li, Limin Yin, Yunqing Gu, Xuefeng Dou, Haipeng Sun, Wei Wang, Junli Liu

{"title":"Pyruvate metabolism enzyme DLAT promotes tumorigenesis by suppressing leucine catabolism","authors":"Ning Wang, Sijia Lu, Ziyi Cao, Huimin Li, Junting Xu, Qian Zhou, Hanrui Yin, Qiqi Qian, Xianjing Zhang, Mijia Tao, Quanxin Jiang, Peihui Zhou, Liaoyuan Zheng, Liu Han, Hongtao Li, Limin Yin, Yunqing Gu, Xuefeng Dou, Haipeng Sun, Wei Wang, Junli Liu","doi":"10.1016/j.cmet.2025.02.008","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.02.008","url":null,"abstract":"Pyruvate and branched-chain amino acid (BCAA) metabolism are pivotal pathways in tumor progression, yet the intricate interplay between them and its implications for tumor progression remain elusive. Our research reveals that dihydrolipoamide S-acetyltransferase (DLAT), a pyruvate metabolism enzyme, promotes leucine accumulation and sustains mammalian target of rapamycin (mTOR) complex activation in hepatocellular carcinoma (HCC). Mechanistically, DLAT directly acetylates the K109 residue of AU RNA-binding methylglutaconyl-coenzyme A (CoA) hydratase (AUH), a critical enzyme in leucine catabolism, inhibiting its activity and leading to leucine accumulation. Notably, DLAT upregulation correlates with poor prognosis in patients with HCC. Therefore, we developed an AUHK109R-mRNA lipid nanoparticles (LNPs) therapeutic strategy, which effectively inhibits tumor growth by restoring leucine catabolism and inhibiting mTOR activation in vivo. In summary, our findings uncover DLAT’s unexpected role as an acetyltransferase for AUH, suppressing leucine catabolism. Restoring leucine catabolism with AUHK109R-mRNA LNP effectively inhibits HCC development, highlighting a novel direction for cancer research.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"214 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dietary timing enhances exercise by modulating fat-muscle crosstalk via adipocyte AMPKα2 signaling 饮食时间通过脂肪细胞AMPKα2信号调节脂肪-肌肉串扰来增强运动

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-14 DOI: 10.1016/j.cmet.2025.02.007

Jianghui Chen, Jing Xiang, Meiyu Zhou, Rongfeng Huang, Jianxin Zhang, Yuanting Cui, Xiaoqing Jiang, Yang Li, Runchao Zhou, Haoran Xin, Jie Li, Lihua Li, Sin Man Lam, Jianfang Zhu, Yanxiu Chen, Qingyuan Yang, Zhifu Xie, Guanghou Shui, Fang Deng, Zhihui Zhang, Min-Dian Li

{"title":"Dietary timing enhances exercise by modulating fat-muscle crosstalk via adipocyte AMPKα2 signaling","authors":"Jianghui Chen, Jing Xiang, Meiyu Zhou, Rongfeng Huang, Jianxin Zhang, Yuanting Cui, Xiaoqing Jiang, Yang Li, Runchao Zhou, Haoran Xin, Jie Li, Lihua Li, Sin Man Lam, Jianfang Zhu, Yanxiu Chen, Qingyuan Yang, Zhifu Xie, Guanghou Shui, Fang Deng, Zhihui Zhang, Min-Dian Li","doi":"10.1016/j.cmet.2025.02.007","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.02.007","url":null,"abstract":"Feeding rhythms regulate exercise performance and muscle energy metabolism. However, the mechanisms regulating adipocyte functions remain unclear. Here, using multi-omics analyses, involving (phospho-)proteomics and lipidomics, we found that day-restricted feeding (DRF) regulates diurnal rhythms of the mitochondrial proteome, neutral lipidome, and nutrient-sensing pathways in mouse gonadal white adipose tissue (GWAT). Adipocyte-specific knockdown of Prkaa2 (the gene encoding AMPKα2) impairs physical endurance. This defect is associated with altered rhythmicity in acyl-coenzyme A (CoA) metabolism-related genes, a loss of rhythmicity in the GWAT lipidome, and circadian remodeling of serum metabolites—in particular, lactate and succinate. We also found that adipocyte Prkaa2 regulates muscle clock genes during DRF. Notably, oral administration of the AMPK activator C29 increases endurance and muscle functions in a time-of-day manner, which requires intact adipocyte AMPKα2 signaling. Collectively, our work defines adipocyte AMPKα2 signaling as a critical regulator of circadian metabolic coordination between fat and muscle, thereby enhancing exercise performance.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"8 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Seeing the world through the eyes of cultured cells 通过培养细胞的眼睛看世界

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-12 DOI: 10.1016/j.cmet.2025.01.027

Joycelyn Tan, Guy B. Kunzmann, Sam Virtue, Jason R. Cantor, Daniel J. Fazakerley

引用次数: 0

A key role of PIEZO2 mechanosensitive ion channel in adipose sensory innervation PIEZO2机械敏感离子通道在脂肪感觉神经支配中的关键作用

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-06 DOI: 10.1016/j.cmet.2025.02.004

Yu Wang, Yunxiao Zhang, Verina H. Leung, Saba Heydari Seradj, Utku Sonmez, M. Rocio Servin-Vences, Shuke Xiao, Xiangyu Ren, Leon Wang, Sassan A. Mishkanian, Sejal A. Kini, Jonathan Z. Long, Darren J. Lipomi, Li Ye, Ardem Patapoutian

{"title":"A key role of PIEZO2 mechanosensitive ion channel in adipose sensory innervation","authors":"Yu Wang, Yunxiao Zhang, Verina H. Leung, Saba Heydari Seradj, Utku Sonmez, M. Rocio Servin-Vences, Shuke Xiao, Xiangyu Ren, Leon Wang, Sassan A. Mishkanian, Sejal A. Kini, Jonathan Z. Long, Darren J. Lipomi, Li Ye, Ardem Patapoutian","doi":"10.1016/j.cmet.2025.02.004","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.02.004","url":null,"abstract":"Compared with the well-established functions of sympathetic innervation, the role of sensory afferents in adipose tissues remains less understood. Recent work has revealed the anatomical and physiological significance of adipose sensory innervation; however, its molecular underpinning remains unclear. Here, using organ-targeted single-cell RNA sequencing, we identified the mechanoreceptor PIEZO2 as one of the most prevalent receptors in fat-innervating dorsal root ganglia (DRG) neurons. PIEZO2 deletion in fat-innervating neurons induced transcriptional programs in adipose tissue resembling sympathetic activation, mirroring DRG ablation. Conversely, a gain-of-function PIEZO2 mutant shifted the adipose phenotypes in the opposite direction. These results indicate that PIEZO2 plays a major role in the sensory regulation of adipose tissues. This discovery opens new avenues for exploring mechanosensation in organs not traditionally considered mechanically active, such as adipose tissues, and therefore sheds light on the broader significance of mechanosensation in regulating organ function and homeostasis.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"44 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ferroptosis in adipose tissue: A promising pathway for treating obesity? 脂肪组织中的铁下垂：治疗肥胖的一个有希望的途径？

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-04 DOI: 10.1016/j.cmet.2025.01.029

John R. Speakman

引用次数: 0

Testing the carbohydrate-insulin model: Short-term metabolic responses to consumption of meals with varying glycemic index in healthy adults 测试碳水化合物-胰岛素模型：健康成人食用不同血糖指数食物的短期代谢反应

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-04 DOI: 10.1016/j.cmet.2025.01.015

Ying Liu, Huihui Mei, Li Xue, Chuanli Cheng, Yingtong Wu, Chao Zou, Ying Yu, Lin Gao, Huanan Zhang, Xinrui Gao, Qiang Li, Lu Wang, Jie Liu, Chaoqun Niu, Xueying Zhang, Sumei Hu, John R. Speakman

{"title":"Testing the carbohydrate-insulin model: Short-term metabolic responses to consumption of meals with varying glycemic index in healthy adults","authors":"Ying Liu, Huihui Mei, Li Xue, Chuanli Cheng, Yingtong Wu, Chao Zou, Ying Yu, Lin Gao, Huanan Zhang, Xinrui Gao, Qiang Li, Lu Wang, Jie Liu, Chaoqun Niu, Xueying Zhang, Sumei Hu, John R. Speakman","doi":"10.1016/j.cmet.2025.01.015","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.01.015","url":null,"abstract":"The carbohydrate-insulin model predicts that meals with varying glycemic indices will elicit distinct metabolic and hunger responses, including greater intake at subsequent meals following high-glycemic-index meals. To test this, a randomized trial (NCT05804942) was conducted in healthy adults using intervention meals with low, medium, and high glycemic indices and a constant macronutrient composition. After intake of the intervention meals, glucose and insulin followed the predicted pattern, but subjective hunger did not. At the group level, low glycemic index meals led to lower energy intake changes. At the individual level, energy intake changes were unrelated to body fatness or levels of glucose, β-hydroxybutyrate, free fatty acids, L-lactate, leptin, adrenaline, glucagon-like peptide-1, glucagon, and insulin-glucagon ratio. A weak negative association was observed between energy intake changes and insulin or insulin-glucagon ratio at 300 min, opposite to the model’s prediction. These data provide little support for the carbohydrate-insulin model.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"34 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

“Shunt-ing” down obesity with novel endogenous metabolites 用新的内源性代谢物“分流”肥胖

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-04 DOI: 10.1016/j.cmet.2025.02.005

Victor J. Pai, Alan Saghatelian

引用次数: 0

A cellular and molecular basis of leptin resistance 瘦素抵抗的细胞和分子基础

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-04 DOI: 10.1016/j.cmet.2025.01.001

Bowen Tan, Kristina Hedbacker, Leah Kelly, Zhaoyue Zhang, Alexandre Moura-Assis, Ji-Dung Luo, Joshua D. Rabinowitz, Jeffrey M. Friedman

引用次数: 0

Brain dopamine responses to ultra-processed milkshakes are highly variable and not significantly related to adiposity in humans 脑多巴胺对超加工奶昔的反应是高度可变的，与人类肥胖没有显著关系

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-04 DOI: 10.1016/j.cmet.2025.02.002

Valerie L. Darcey, Juen Guo, Meible Chi, Stephanie T. Chung, Amber B. Courville, Isabelle Gallagher, Peter Herscovitch, Paule V. Joseph, Rebecca Howard, Melissa La Noire, Lauren Milley, Alex Schick, Michael Stagliano, Sara Turner, Nicholas Urbanski, Shanna Yang, Nan Zhai, Megan S. Zhou, Kevin D. Hall

{"title":"Brain dopamine responses to ultra-processed milkshakes are highly variable and not significantly related to adiposity in humans","authors":"Valerie L. Darcey, Juen Guo, Meible Chi, Stephanie T. Chung, Amber B. Courville, Isabelle Gallagher, Peter Herscovitch, Paule V. Joseph, Rebecca Howard, Melissa La Noire, Lauren Milley, Alex Schick, Michael Stagliano, Sara Turner, Nicholas Urbanski, Shanna Yang, Nan Zhai, Megan S. Zhou, Kevin D. Hall","doi":"10.1016/j.cmet.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.02.002","url":null,"abstract":"Ultra-processed foods high in fat and sugar have been theorized to be addictive due to their purported ability to induce an exaggerated post-ingestive brain dopamine response akin to drugs of abuse. Using [11C]raclopride positron emission tomography (PET) displacement methods used to measure brain dopamine responses to addictive drugs, we measured striatal dopamine responses beginning 30 min after ingesting an ultra-processed milkshake high in fat and sugar in 50 young, healthy adults over a wide body mass index (BMI) range (20–45 kg/m2). Surprisingly, milkshake consumption did not result in a significant post-ingestive dopamine response in the striatum (p = 0.62) nor in any striatal subregion (p > 0.33), and the highly variable interindividual responses were not significantly related to adiposity (BMI: r = 0.076, p = 0.51; % body fat: r = 0.16, p = 0.28). Thus, post-ingestive striatal dopamine responses to an ultra-processed milkshake were likely substantially smaller than for many addictive drugs and below the limits of detection using standard PET methods.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"23 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0