Life metabolism最新文献_第4页

BET inhibition induces GDH1-dependent glutamine metabolic remodeling and vulnerability in liver cancer. BET抑制诱导肝癌gdh1依赖性谷氨酰胺代谢重塑和易感性。

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

引用次数: 0

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

引用次数: 0

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. MRE11乳酸化：Warburg效应与DNA修复之间的联系。

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

Pingyu Liu, Hongbin Ji, Fuming Li

引用次数: 0

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

引用次数: 0

Results of the Second Life Metabolism Travel Awards 2024 2024 年第二人生代谢旅行奖评选结果

Life metabolism Pub Date : 2024-03-20 DOI: 10.1093/lifemeta/loae007

John R. Speakman

引用次数: 0

Apolipoprotein A-IV and its derived peptide, T55−121, improve glycemic control and increase energy expenditure 载脂蛋白 A-IV 及其衍生肽 T55-121 可改善血糖控制并增加能量消耗

Life metabolism Pub Date : 2024-03-14 DOI: 10.1093/lifemeta/loae010

Zhen Cao, Lei Lei, Ziyun Zhou, Shimeng Xu, Linlin Wang, Weikang Gong, Qi Zhang, Bin Pan, Gaoxin Zhang, Quan Yuan, Liujuan Cui, Min Zheng, Tao Xu, You Wang, Shuyan Zhang, Pingsheng Liu

{"title":"Apolipoprotein A-IV and its derived peptide, T55−121, improve glycemic control and increase energy expenditure","authors":"Zhen Cao, Lei Lei, Ziyun Zhou, Shimeng Xu, Linlin Wang, Weikang Gong, Qi Zhang, Bin Pan, Gaoxin Zhang, Quan Yuan, Liujuan Cui, Min Zheng, Tao Xu, You Wang, Shuyan Zhang, Pingsheng Liu","doi":"10.1093/lifemeta/loae010","DOIUrl":"https://doi.org/10.1093/lifemeta/loae010","url":null,"abstract":"\u0000 It is crucial to understand the glucose control within our bodies. Bariatric/metabolic surgeries, including laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB), provide an avenue for exploring the potential key factors involved in maintaining glucose homeostasis since these surgeries have shown promising results in improving glycemic control among patients with severe type 2 diabetes (T2D). For the first time, a markedly altered population of serum proteins in patients after LSG was discovered and analyzed through proteomics. Apolipoprotein A-IV (apoA-IV) was revealed to be increased dramatically in diabetic obese patients following LSG, and a similar effect was observed in patients after RYGB surgery. Moreover, recombinant protein apoA-IV treatment was proven to enhance insulin secretion in isolated human islets. These results showed that apoA-IV may play a crucial role in glycemic control in humans, potentially through enhancing insulin secretion in human islets. ApoA-IV was further shown to enhance energy expenditure and improve glucose tolerance in diabetic rodents, through stimulating glucose-dependent insulin secretion in pancreatic β cells, partially via Gαs-coupled GPCR/cAMP (G protein-coupled receptor-cyclic adenosine monophosphate) signaling. Furthermore, T55−121, truncated peptide 55−121 of apoA-IV, was discovered to mediate the function of apoA-IV. These collective findings contribute to our understanding of the relationship between apoA-IV and glycemic control, highlighting its potential as a biomarker or therapeutic target in managing and improving glucose regulation.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"16 1part1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140242935","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

Alternate day fasting aggravates atherosclerosis through the suppression of hepatic ATF3 in Apoe −/− mice 隔日禁食通过抑制载脂蛋白-/-小鼠肝脏 ATF3 使动脉粥样硬化恶化

Life metabolism Pub Date : 2024-03-07 DOI: 10.1093/lifemeta/loae009

Yajuan Deng, Xiaoyu Yang, Xueru Ye, Youwen Yuan, Yanan Zhang, Fei Teng, Danming You, Xuan Zhou, Wenhui Liu, Kangli Li, Shenjian Luo, Zhi Yang, Ruxin Chen, Guojun Shi, Jin Li, Huijie Zhang

{"title":"Alternate day fasting aggravates atherosclerosis through the suppression of hepatic ATF3 in Apoe\u0000 −/− mice","authors":"Yajuan Deng, Xiaoyu Yang, Xueru Ye, Youwen Yuan, Yanan Zhang, Fei Teng, Danming You, Xuan Zhou, Wenhui Liu, Kangli Li, Shenjian Luo, Zhi Yang, Ruxin Chen, Guojun Shi, Jin Li, Huijie Zhang","doi":"10.1093/lifemeta/loae009","DOIUrl":"https://doi.org/10.1093/lifemeta/loae009","url":null,"abstract":"\u0000 Atherosclerosis is the major contributor to cardiovascular mortality worldwide. Alternate day fasting (ADF) has gained growing attention due to its metabolic benefits. However, the effects of ADF on atherosclerotic plaque formation remain inconsistent and controversial in atherosclerotic animal models. The present study was designed to investigate the effect of ADF on atherosclerosis in apolipoprotein E-deficient (Apoe−/−) mice. Eleven-week-old male Apoe−/− mice fed with Western diet (WD) were randomly grouped into ad libitum (AL) group and ADF group, and ADF aggravated both the early and advanced atherosclerotic lesion formation, which might be due to the disturbed cholesterol profiles caused by ADF intervention. ADF significantly altered cholesterol metabolism pathways and down-regulated integrated stress response (ISR) in the liver. The hepatic expression of activating transcription factor 3 (ATF3) was suppressed in mice treated with ADF and hepatocyte-specific overexpression of ATF3 attenuated the effects of ADF on atherosclerotic plaque formation in Apoe−/− mice. Moreover, the expression of ATF3 could be regulated by Krüppel-like factor 6 (KLF6) and both the expressions of ATF3 and KLF6 were regulated by hepatic cellular ISR pathway. In conclusion, ADF aggravates atherosclerosis progression in Apoe−/− mice fed on WD. ADF inhibits the hepatic ISR signaling pathway and decreases the expression of KLF6, subsequently inhibiting ATF3 expression. The suppressed ATF3 expression in the liver mediates the deteriorated effects of ADF on atherosclerosis in Apoe−/− mice. The findings suggest the potentially harmful effects when ADF intervention is applied to the population at high risk of atherosclerosis.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"24 105","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140260034","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

Lipid-derived radical-trapping antioxidants suppress ferroptosis. 源于脂质的自由基捕获抗氧化剂可抑制铁蛋白沉积。

Life metabolism Pub Date : 2024-03-06 eCollection Date: 2024-04-01 DOI: 10.1093/lifemeta/loae008

Ruoxi Zhang, Guido Kroemer, Daolin Tang

引用次数: 0