Life metabolism最新文献_第3页

Genome-wide CRISPR screens identify PTPN21 and WDR26 as modulators of the mitochondrial stress-induced ISR.

Life metabolism Pub Date : 2024-05-28 eCollection Date: 2024-08-01 DOI: 10.1093/lifemeta/loae020

Wen Li, Mingyue Dong, Kaiyu Gao, Jialiang Guan, Ying Liu

引用次数: 0

Life metabolism Pub Date : 2024-05-24 eCollection Date: 2024-08-01 DOI: 10.1093/lifemeta/loae019

Callen C Goldsmith, Garron T Dodd

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Fatty acid oxidation-induced HIF-1α activation facilitates hepatic urate synthesis through upregulating NT5C2 and XDH 脂肪酸氧化诱导的 HIF-1α 激活通过上调 NT5C2 和 XDH 促进肝脏尿酸盐合成

Life metabolism Pub Date : 2024-05-17 DOI: 10.1093/lifemeta/loae018

Ningning Liang, Xuan Yuan, Lili Zhang, Xia Shen, Shanshan Zhong, Luxiao Li, Rui Li, Xiaodong Xu, Xin Chen, Chunzhao Yin, Shuyuan Guo, Jing Ge, Mingjiang Zhu, Yongzhen Tao, Shiting Chen, Yongbing Qian, Nicola Dalbeth, Tony R. Merriman, R. Terkeltaub, Changgui Li, Qiang Xia, Huiyong Yin

{"title":"Fatty acid oxidation-induced HIF-1α activation facilitates hepatic urate synthesis through upregulating NT5C2 and XDH","authors":"Ningning Liang, Xuan Yuan, Lili Zhang, Xia Shen, Shanshan Zhong, Luxiao Li, Rui Li, Xiaodong Xu, Xin Chen, Chunzhao Yin, Shuyuan Guo, Jing Ge, Mingjiang Zhu, Yongzhen Tao, Shiting Chen, Yongbing Qian, Nicola Dalbeth, Tony R. Merriman, R. Terkeltaub, Changgui Li, Qiang Xia, Huiyong Yin","doi":"10.1093/lifemeta/loae018","DOIUrl":"https://doi.org/10.1093/lifemeta/loae018","url":null,"abstract":"\u0000 Dyslipidemia affects approximately half of all people with gout, and prior Mendelian randomization analysis suggested a causal role for elevated triglycerides in hyperuricemia (HU), but the underlying mechanisms remain elusive. We hypothesize that dyslipidemia promotes hepatic urate biosynthesis in HU and gout and fatty acid (FA) oxidation (FAO) drives this process. Here we developed a targeted metabolomics to quantify major metabolites in purine metabolic pathway in the sera of a human cohort with HU, gout, and normaluricemic controls. We found that the levels of major purine metabolites and multiple FAs were significantly elevated in HU and gout, compared to normouricemic controls, whereas hypoxathine showed opposite trend. Furthermore, the levels of multiple serum FAs were positively correlated with urate, xanthine, and inosine but negatively with hypoxanthine, which was also observed in a murine model of high-fat diet-induced HU. Using a stable isotope labeled metabolic flux assay, we discovered that exogenous hypoxanthine plays a key role in urate synthesis. Moreover, FAO-induced hypoxia-inducible factor 1 alpha (HIF-1α) activation upregulated 5’-nucleotidase II (NT5C2) and xanthine dehydrogenase (XDH) levels to facilitate hypoxanthine uptake from blood to liver and activation of urate biosynthesis. Our findings was further supported by data in human hepatocytes and 50 paired serum and liver tissues from liver transplant donors.Together, this study uncovers a mechanism by which FAO promotes hepatic urate synthesis by activating HIF-1α-NT5C2/XDH pathways, directly linking lipid metabolism to HU.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"2 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140963036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hypoxia makes EZH2 inhibitor not easy—advances of crosstalk between HIF and EZH2 缺氧使 EZH2 抑制剂难以发挥作用--HIF 与 EZH2 之间的相互影响

Life metabolism Pub Date : 2024-05-06 DOI: 10.1093/lifemeta/loae017

Zhanya Huang, Yuanjun Tang, Jianlin Zhang, Jiaqi Huang, Rui Cheng, Yunyun Guo, Celina G Kleer, Yuqing Wang, Lixiang Xue

引用次数: 0

BET inhibition induces GDH1-dependent glutamine metabolic remodeling and vulnerability in liver cancer.

Life metabolism Pub Date : 2024-04-26 eCollection Date: 2024-08-01 DOI: 10.1093/lifemeta/loae016

Wen Mi, Jianwei You, Liucheng Li, Lingzhi Zhu, Xinyi Xia, Li Yang, Fei Li, Yi Xu, Junfeng Bi, Pingyu Liu, Li Chen, Fuming Li

{"title":"BET inhibition induces GDH1-dependent glutamine metabolic remodeling and vulnerability in liver cancer.","authors":"Wen Mi, Jianwei You, Liucheng Li, Lingzhi Zhu, Xinyi Xia, Li Yang, Fei Li, Yi Xu, Junfeng Bi, Pingyu Liu, Li Chen, Fuming Li","doi":"10.1093/lifemeta/loae016","DOIUrl":"10.1093/lifemeta/loae016","url":null,"abstract":"Bromodomain and extra-terminal domain (BET) proteins, which function partly through MYC proto-oncogene (MYC), are critical epigenetic readers and emerging therapeutic targets in cancer. Whether and how BET inhibition simultaneously induces metabolic remodeling in cancer cells remains unclear. Here we find that even transient BET inhibition by JQ-1 and other pan-BET inhibitors (pan-BETis) blunts liver cancer cell proliferation and tumor growth. BET inhibition decreases glycolytic gene expression but enhances mitochondrial glucose and glutamine oxidative metabolism revealed by metabolomics and isotope labeling analysis. Specifically, BET inhibition downregulates miR-30a to upregulate glutamate dehydrogenase 1 (GDH1) independent of MYC, which produces α-ketoglutarate for mitochondrial oxidative phosphorylation (OXPHOS). Targeting GDH1 or OXPHOS is synthetic lethal to BET inhibition, and combined BET and OXPHOS inhibition therapeutically prevents liver tumor growth in vitro and in vivo. Together, we uncover an important epigenetic-metabolic crosstalk whereby BET inhibition induces MYC-independent and GDH1-dependent glutamine metabolic remodeling that can be exploited for innovative combination therapy of liver cancer.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"3 4","pages":"loae016"},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intermittent fasting-a double edged sword for atherosclerosis. 间歇性禁食--动脉粥样硬化的双刃剑。

Life metabolism Pub Date : 2024-04-25 eCollection Date: 2024-06-01 DOI: 10.1093/lifemeta/loae015

Jacques Togo, Hoon-Ki Sung

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Probing and imaging phospholipid dynamics in live cells 活细胞中磷脂动态的探测和成像

Life metabolism Pub Date : 2024-04-13 DOI: 10.1093/lifemeta/loae014

Zhongsheng Wu, Yongtao Du, Tom Kirchhausen, Kangmin He

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High temperature ameliorates high-fat diet-induced obesity by promoting ceramide breakdown in skeletal muscle tissue 高温通过促进骨骼肌组织中神经酰胺的分解，改善高脂饮食诱发的肥胖症

Life metabolism Pub Date : 2024-04-03 DOI: 10.1093/lifemeta/loae012

Qiankun Wang, Lupeng Chen, Junzhi Zhang, Yue Liu, Yi Jin, Jian Wu, Zhuqing Ren

{"title":"High temperature ameliorates high-fat diet-induced obesity by promoting ceramide breakdown in skeletal muscle tissue","authors":"Qiankun Wang, Lupeng Chen, Junzhi Zhang, Yue Liu, Yi Jin, Jian Wu, Zhuqing Ren","doi":"10.1093/lifemeta/loae012","DOIUrl":"https://doi.org/10.1093/lifemeta/loae012","url":null,"abstract":"\u0000 Obesity is considered an epidemic often accompanied by insulin resistance (IR). Heat treatment (HT) has been shown to prevent high-fat diet-induced IR in skeletal muscle, but the underlying mechanisms are poorly understood. In this study, we discovered that high temperature alleviated the hallmarks of obesity by promoting glycogen synthesis and lowering blood glucose levels in skeletal muscle tissue (SMT). Additionally, HT maintained the decay phase of heat shock factor 1 (HSF1), leading to the activation of gene expression of heat shock proteins (HSPs), which contributed to the alleviation of IR in SMT of diet-induced obese (DIO) mice. Metabolomics and lipidomics analyses showed that HT promoted ceramide (Cer) breakdown, resulting in an elevation of both sphingomyelin (SM) and sphingosine, which further contributed to the amelioration of IR in SMT of DIO mice. Importantly, the increase in sphingosine was attributed to the heightened expression of the acid ceramidase N-acylsphingosine amidohydrolase 1 (ASAH1), and the inhibition of ASAH1 attenuated HT-relieved IR in SMT of DIO mice. Surprisingly, high temperature increased the composition of Cer and cholesteryl ester in lipid droplets of skeletal muscle cells. This not only helped alleviate IR but also prevented lipotoxicity in SMT of DIO mice. These findings revealed a previously unknown connection between a high-temperature environment and sphingolipid metabolism in obesity, suggesting that high temperature can improve IR by promoting Cer catabolism in SMT of obese mice.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"100 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140748777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MRE11 lactylation: a linker between Warburg effect and DNA repair.

Life metabolism Pub Date : 2024-04-02 eCollection Date: 2024-06-01 DOI: 10.1093/lifemeta/loae013

Pingyu Liu, Hongbin Ji, Fuming Li

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IL-10 suppresses lipid metabolism-mediated intestinal inflammation IL-10 可抑制脂质代谢介导的肠道炎症

Life metabolism Pub Date : 2024-03-26 DOI: 10.1093/lifemeta/loae011

Tristram A J Ryan, Ivan Zanoni

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