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Gut bacterial metabolism produces neuroactive steroids in pregnant women 孕妇肠道细菌代谢产生神经活性类固醇
Life metabolism Pub Date : 2024-07-19 DOI: 10.1093/lifemeta/loae030
Kelsey E Huus, Ruth E. Ley
{"title":"Gut bacterial metabolism produces neuroactive steroids in pregnant women","authors":"Kelsey E Huus, Ruth E. Ley","doi":"10.1093/lifemeta/loae030","DOIUrl":"https://doi.org/10.1093/lifemeta/loae030","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141822033","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
Potential therapeutic strategies for MASH: from preclinical to clinical development MASH 的潜在治疗策略：从临床前研究到临床开发
Life metabolism Pub Date : 2024-07-06 DOI: 10.1093/lifemeta/loae029
Zhifu Xie, Yufeng Li, Long Cheng, Yidan Huang, Wanglin Rao, Honglu Shi, Jingya Li
{"title":"Potential therapeutic strategies for MASH: from preclinical to clinical development","authors":"Zhifu Xie, Yufeng Li, Long Cheng, Yidan Huang, Wanglin Rao, Honglu Shi, Jingya Li","doi":"10.1093/lifemeta/loae029","DOIUrl":"https://doi.org/10.1093/lifemeta/loae029","url":null,"abstract":"\u0000 Current treatment paradigms for metabolic dysfunction-associated steatohepatitis (MASH) are based primarily on dietary restrictions and the use of existing drugs, including anti-diabetic and anti-obesity medications. However, given the limited number of approved drugs specifically for MASH, recent efforts have focused on promising strategies that specifically target hepatic lipid metabolism, inflammation, fibrosis, or a combination of these processes. In this review, we examined the pathophysiology underlying the development of MASH in relation to recent advances in effective MASH therapy. Particularly, we analyzed the effects of lipogenesis inhibitors, nuclear receptor agonists, glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists, fibroblast growth factor mimetics, and combinatorial therapeutic approaches. We summarize these targets along with their preclinical and clinical candidates with the ultimate goal of optimizing the therapeutic prospects for MASH.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141671861","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
Immuno-electron microscopy localizes Caenorhabditis elegans vitellogenins along the classic exocytosis route 免疫电子显微镜确定秀丽隐杆线虫卵黄原蛋白的经典外渗路线
Life metabolism Pub Date : 2024-06-13 DOI: 10.1093/lifemeta/loae025
Chao Zhai, Nan Zhang, Xixia Li, Xue-Ke Tan, Fei Sun, Meng-Qiu Dong
{"title":"Immuno-electron microscopy localizes Caenorhabditis elegans vitellogenins along the classic exocytosis route","authors":"Chao Zhai, Nan Zhang, Xixia Li, Xue-Ke Tan, Fei Sun, Meng-Qiu Dong","doi":"10.1093/lifemeta/loae025","DOIUrl":"https://doi.org/10.1093/lifemeta/loae025","url":null,"abstract":"\u0000 Vitellogenins (VITs) are the most abundant proteins in adult hermaphrodite Caenorhabditis elegans. VITs are synthesized in the intestine, secreted to the pseudocoelom, matured into yolk proteins, and finally deposited in oocytes as nutrients for progeny developme nt. How VITs are secreted out of the intestine remains unclear. Using immuno-electron microscopy (immuno-EM), we localize intestinal VITs along an exocytic pathway consisting of the rough endoplasmic reticulum (ER), the Golgi, and the lipid bilayer-bounded VIT vesicles (VVs). This suggests that the classic exocytotic pathway mediates the secretion of VITs from the intestine to the pseudocoelom. We also show that pseudocoelomic yolk patches (PYPs) are membrane-less and amorphous. The different VITs/yolk proteins are packed as a mixture into the above structures. The size of VVs can vary with the VIT levels and the age of the worm. On adult day 2 (AD 2), intestinal VVs (~200 nm in diameter) are smaller than gonadal yolk organelles (YOs, ~500 nm in diameter). VVs, PYPs, and YOs share a uniform medium electron density by conventional EM. The morphological profiles documented in this study serve as a reference for future studies of VITs/yolk proteins.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141346708","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
Protecting liver health with microbial-derived succinylated bile acids 用微生物提取的琥珀酰化胆汁酸保护肝脏健康
Life metabolism Pub Date : 2024-06-13 DOI: 10.1093/lifemeta/loae023
H. Demagny, A. Perino, Kristina Schoonjans
{"title":"Protecting liver health with microbial-derived succinylated bile acids","authors":"H. Demagny, A. Perino, Kristina Schoonjans","doi":"10.1093/lifemeta/loae023","DOIUrl":"https://doi.org/10.1093/lifemeta/loae023","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141347959","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
Cholesin, a new hormone bridges intestinal cholesterol absorption and hepatic synthesis 胆固醇素--一种连接肠道胆固醇吸收和肝脏合成的新激素
Life metabolism Pub Date : 2024-06-07 DOI: 10.1093/lifemeta/loae024
Peter U Amadi, Da-wei Zhang
{"title":"Cholesin, a new hormone bridges intestinal cholesterol absorption and hepatic synthesis","authors":"Peter U Amadi, Da-wei Zhang","doi":"10.1093/lifemeta/loae024","DOIUrl":"https://doi.org/10.1093/lifemeta/loae024","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141372758","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
Downregulation of RhoA/ROCK1/YAP/F-actin causing decreased aortic smooth muscle cell stiffness promotes aortic dissection formation RhoA/ROCK1/YAP/F-actin 的下调导致主动脉平滑肌细胞硬度下降，从而促进主动脉夹层的形成
Life metabolism Pub Date : 2024-06-03 DOI: 10.1093/lifemeta/loae022
Wei Zhang, Mengxiao Wang, Enci Wang, Wei Lu, Zengxia Li, Yuchong Zhang, Gaofei Hu, Qi Zhang, Wenxin Shan, Yongjun Dang, Zhe Zhao, Lemin Zheng, Weiguo Fu, Lixin Wang
{"title":"Downregulation of RhoA/ROCK1/YAP/F-actin causing decreased aortic smooth muscle cell stiffness promotes aortic dissection formation","authors":"Wei Zhang, Mengxiao Wang, Enci Wang, Wei Lu, Zengxia Li, Yuchong Zhang, Gaofei Hu, Qi Zhang, Wenxin Shan, Yongjun Dang, Zhe Zhao, Lemin Zheng, Weiguo Fu, Lixin Wang","doi":"10.1093/lifemeta/loae022","DOIUrl":"https://doi.org/10.1093/lifemeta/loae022","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141269273","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
The energetics of cellular life transitions. 细胞生命转换的能量学。
Life metabolism Pub Date : 2024-06-01 Epub Date: 2023-12-27 DOI: 10.1093/lifemeta/load051
Anna S Monzel, Michael Levin, Martin Picard
{"title":"The energetics of cellular life transitions.","authors":"Anna S Monzel, Michael Levin, Martin Picard","doi":"10.1093/lifemeta/load051","DOIUrl":"10.1093/lifemeta/load051","url":null,"abstract":"<p><p>Major life transitions are always difficult because change costs energy. Recent findings have demonstrated how mitochondrial oxidative phosphorylation (OxPhos) defects increase the energetic cost of living, and that excessive integrated stress response (ISR) signaling may prevent cellular identity transitions during development. In this perspective, we discuss general bioenergetic principles of life transitions and the costly molecular processes involved in reprograming the cellular hardware/software as cells shift identity. The energetic cost of cellular differentiation has not been directly quantified, representing a gap in knowledge. We propose that the ISR is an energetic checkpoint evolved to i) prevent OxPhos-deficient cells from engaging in excessively costly transitions, and ii) allow ISR-positive cells to recruit systemic energetic resources by signaling via the brain.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10984639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857419","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
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":null,"pages":null},"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
{"title":"Hypoxia makes EZH2 inhibitor not easy—advances of crosstalk between HIF and EZH2","authors":"Zhanya Huang, Yuanjun Tang, Jianlin Zhang, Jiaqi Huang, Rui Cheng, Yunyun Guo, Celina G Kleer, Yuqing Wang, Lixiang Xue","doi":"10.1093/lifemeta/loae017","DOIUrl":"https://doi.org/10.1093/lifemeta/loae017","url":null,"abstract":"\u0000 Histone methylation plays a crucial role in tumorigenesis. Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that regulates chromatin structure and gene expression. EZH2 inhibitors (EZH2is) have been shown to be effective in treating hematologic malignancies, while their effectiveness in solid tumors remains limited. One of the major challenges in the treatment of solid tumors is their hypoxic tumor microenvironment. Hypoxia-inducible factor 1-alpha (HIF-1α) is a key hypoxia responder that interacts with EZH2 to promote tumor progression. Here we discuss the implications of the relationship between EZH2 and hypoxia for expanding the application of EZH2is in solid tumors.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141010100","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
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
{"title":"Probing and imaging phospholipid dynamics in live cells","authors":"Zhongsheng Wu, Yongtao Du, Tom Kirchhausen, Kangmin He","doi":"10.1093/lifemeta/loae014","DOIUrl":"https://doi.org/10.1093/lifemeta/loae014","url":null,"abstract":"\u0000 Distinct phospholipid species display specific distribution patterns across cellular membranes, important for their structural and signaling roles and for preserving the integrity and functionality of the plasma membrane and organelles. Recent advancements in lipid biosensor technology and imaging modalities now allow for direct observation of phospholipid distribution, trafficking, and dynamics in living cells. These innovations have markedly advanced our understanding of phospholipid function and regulation at both cellular and subcellular levels. Herein, we summarize the latest developments in phospholipid biosensor design and application, emphasizing the contribution of cutting-edge imaging techniques to elucidating phospholipid dynamics and distribution with unparalleled spatiotemporal precision.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140706947","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
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