Life metabolism最新文献_第8页

TMEM251, a new player in lysosomal enzyme trafficking TMEM251，溶酶体酶运输的新参与者

Life metabolism Pub Date : 2022-12-17 DOI: 10.1093/lifemeta/loac039

Liming Wang, Han-Ming Shen

引用次数: 0

Lipid metabolism in tumor-infiltrating T cells: Mechanisms and applications 肿瘤浸润性T细胞的脂质代谢:机制和应用

Life metabolism Pub Date : 2022-12-15 DOI: 10.1093/lifemeta/loac038

Xin-Yu Ke, Miaowen Zou, Chenqi Xu

{"title":"Lipid metabolism in tumor-infiltrating T cells: Mechanisms and applications","authors":"Xin-Yu Ke, Miaowen Zou, Chenqi Xu","doi":"10.1093/lifemeta/loac038","DOIUrl":"https://doi.org/10.1093/lifemeta/loac038","url":null,"abstract":"\u0000 As an essential part of adaptive immunity, T cells coordinate the immune responses against pathogens and cancer cells. Lipid metabolism has emerged as a key regulator for the activation, differentiation and effector functions of T cells. Therefore, uncovering the molecular mechanisms by which lipid metabolism dictates T cell biology is of vital importance. The tumor microenvironment is a hostile milieu that is often characterized by nutrient restriction. In this environment, various cells, such as T cells and cancer cells, reprogram their metabolism, including their lipid metabolism, to meet their energy and functional needs. Here, we review the participation of fatty acid and cholesterol metabolism homeostasis in orchestrating T cell biology. We demonstrate how the tumor microenvironment reshapes the lipid metabolism in T cells. Importantly, we highlight the current cancer therapeutic interventions that target fatty acid and cholesterol metabolism of T cells. By offering a holistic understanding of how lipid metabolic adaption by T cells facilitates their immunosurveillance in the tumor microenvironment, we believe this review and the future studies might inspire the next-generation immunotherapies.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45538764","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: 2

Circadian metabolism regulates the macrophage inflammatory response 昼夜代谢调节巨噬细胞的炎症反应

Life metabolism Pub Date : 2022-12-09 DOI: 10.1093/lifemeta/loac037

Yulong Sun, Wenjiao Jiang, T. Horng

{"title":"Circadian metabolism regulates the macrophage inflammatory response","authors":"Yulong Sun, Wenjiao Jiang, T. Horng","doi":"10.1093/lifemeta/loac037","DOIUrl":"https://doi.org/10.1093/lifemeta/loac037","url":null,"abstract":"\u0000 Macrophages are an integral part of the innate immune system and coordinate host defense to microbial infections, as well as shaping the remodeling response after tissue injury. Metabolism is now appreciated to be a powerful and pervasive regulator of the identity and function of macrophages. Upon exposure to microbial ligands, macrophage inflammatory activation and the associated induction of phagocytosis, inflammatory responses and other host defense activities are supported by dynamic changes to cellular metabolism. Of note, metabolic activity is robustly regulated in a circadian fashion, with many metabolic processes displaying peak activity in one phase of the circadian cycle and trough activity in an antiphase manner. Here, we review recent findings that suggest that circadian metabolism influences macrophage activities and particularly the inflammatory response. First, we summarize macrophage activities known to display time-of-day dependent variation and their mechanistic basis. Second, we review metabolic processes that have been shown to be rhythmically regulated in macrophages and discuss how such circadian metabolism affects or is likely to affect macrophage activities. Third, we discuss the concept of entrainment of the macrophage clock, and consider how loss of rhythmic regulation of macrophage activities may contribute to pathophysiological conditions like shift work, obesity and aging. Finally, we propose that circadian metabolism can be used to understand the rationale and mechanistic basis of dynamic regulation of inflammatory responses during infection.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44882916","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

Digging the metabolic roots of NASH up 挖掘NASH的代谢根源

Life metabolism Pub Date : 2022-12-06 DOI: 10.1093/lifemeta/loac036

E. Baldelli, A. Lonardo

引用次数: 1

Acetylation of PPARγ in macrophages promotes visceral fat degeneration in obesity. 巨噬细胞中 PPARγ 的乙酰化会促进肥胖症患者内脏脂肪的退化。

Life metabolism Pub Date : 2022-12-01 Epub Date: 2022-11-11 DOI: 10.1093/lifemeta/loac032

Nicole Aaron, Tarik Zahr, Ying He, Lexiang Yu, Brent Mayfield, Utpal B Pajvani, Li Qiang

{"title":"Acetylation of PPARγ in macrophages promotes visceral fat degeneration in obesity.","authors":"Nicole Aaron, Tarik Zahr, Ying He, Lexiang Yu, Brent Mayfield, Utpal B Pajvani, Li Qiang","doi":"10.1093/lifemeta/loac032","DOIUrl":"10.1093/lifemeta/loac032","url":null,"abstract":"Obesity is characterized by chronic, low-grade inflammation, which is driven by macrophage infiltration of adipose tissue. PPARγ is well established to have an anti-inflammatory function in macrophages, but the mechanism that regulates its function in these cells remains to be fully elucidated. PPARγ undergoes post-translational modifications (PTMs), including acetylation, to mediate ligand responses, including on metabolic functions. Here, we report that PPARγ acetylation in macrophages promotes their infiltration into adipose tissue, exacerbating metabolic dysregulation. We generated a mouse line that expresses a macrophage-specific, constitutive acetylation-mimetic form of PPARγ (K293Qflox/flox:LysM-cre, mK293Q) to dissect the role of PPARγ acetylation in macrophages. Upon high-fat diet feeding to stimulate macrophage infiltration into adipose tissue, we assessed the overall metabolic profile and tissue-specific phenotype of the mutant mice, including responses to the PPARγ agonist Rosiglitazone. Macrophage-specific PPARγ K293Q expression promotes proinflammatory macrophage infiltration and fibrosis in epididymal white adipose tissue, but not in subcutaneous or brown adipose tissue, leading to decreased energy expenditure, insulin sensitivity, glucose tolerance, and adipose tissue function. Furthermore, mK293Q mice are resistant to Rosiglitazone-induced improvements in adipose tissue remodeling. Our study reveals that acetylation is a new layer of PPARγ regulation in macrophage activation, and highlights the importance and potential therapeutic implications of such PTMs in regulating metabolism.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10198133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10148745","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

A multi-omic landscape of steatosis-to-NASH progression 脂肪变性与NASH进展的多组学景观

Life metabolism Pub Date : 2022-12-01 DOI: 10.1093/lifemeta/loac034

Liping Xiang, Xiaoyan Li, Yunchen Luo, Bing Zhou, Yuejun Liu, Yao Li, Duojiao Wu, Lijing Jia, Pei-Wu Zhu, M. Zheng, Hua Wang, Yan Lu

{"title":"A multi-omic landscape of steatosis-to-NASH progression","authors":"Liping Xiang, Xiaoyan Li, Yunchen Luo, Bing Zhou, Yuejun Liu, Yao Li, Duojiao Wu, Lijing Jia, Pei-Wu Zhu, M. Zheng, Hua Wang, Yan Lu","doi":"10.1093/lifemeta/loac034","DOIUrl":"https://doi.org/10.1093/lifemeta/loac034","url":null,"abstract":"\u0000 Nonalcoholic steatohepatitis (NASH) has emerged as a major cause of liver failure and hepatocellular carcinoma. Investigations into the molecular mechanisms that underlie steatosis-to-NASH progression is key to understanding the development of NASH pathophysiology. Here, we present comprehensive multi-omic profiles of preclinical animal models to identify genes, non-coding RNAs, proteins and plasma metabolites involved in this progression. In particular, by transcriptomics analysis, we identified Growth Differentiation Factor 3 (GDF3) as a candidate noninvasive biomarker in NASH. Plasma GDF3 levels are associated with hepatic pathological features in patients with NASH, and differences in these levels provide a high diagnostic accuracy of NASH diagnosis (AUROC = 0.90; 95% confidence interval: 0.85-0.95) with a good sensitivity (90.7%) and specificity (86.4%). In addition, by developing integrated proteomic-metabolomic datasets and performing a subsequent pharmacological intervention in a mouse model of NASH we show that ferroptosis may be a potential target to treat NASH. Moreover, by using competing endogenous RNAs network analysis, we found that several miRNAs, including miR-582-5p and miR-292a-3p, and lncRNAs, including XLOC-085738 and XLOC-041531, are associated with steatosis-to-NASH progression. Collectively, our data provide a valuable resource into the molecular characterization of NASH progression, leading to the novel insight that GDF3 may be a potential noninvasive diagnostic biomarker for NASH while further showing that ferroptosis is a therapeutic target for the disease.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44760090","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: 1

Mitochondria as multifaceted regulators of ferroptosis 线粒体作为铁下垂的多方面调节因子

Life metabolism Pub Date : 2022-11-25 DOI: 10.1093/lifemeta/loac035

Jingyi Guo, Yunhao Zhou, Dingfei Liu, Meng Wang, Yi Wu, D. Tang, Xingguo Liu

{"title":"Mitochondria as multifaceted regulators of ferroptosis","authors":"Jingyi Guo, Yunhao Zhou, Dingfei Liu, Meng Wang, Yi Wu, D. Tang, Xingguo Liu","doi":"10.1093/lifemeta/loac035","DOIUrl":"https://doi.org/10.1093/lifemeta/loac035","url":null,"abstract":"\u0000 Mitochondria are well known to be ‘energy factories’ of the cell as they provide intracellular ATP via oxidative phosphorylation. Interestingly, they also function as a ‘cellular suicidal weapon store’ by acting as a key mediator of various forms of regulated cell death, including apoptosis, pyroptosis, necroptosis and ferroptosis. Ferroptosis, distinct from the other types of regulated cell death, is characterized by iron-dependent lipid peroxidation and subsequent plasma membrane rupture. Growing evidence suggests that an impaired ferroptotic response is implicated in various diseases and pathological conditions, and this impaired response is associated with dramatic changes in mitochondrial morphology and function. Mitochondria are the center of iron metabolism and energy production, leading to altered lipid peroxidation sensitivity. Although a growing number of studies have explored the inextricable link between mitochondria and ferroptosis, the role of this organelle in regulating ferroptosis remains unclear. Here, we review recent advances in our understanding of the role of mitochondrial in ferroptosis and summarize the characteristics of this novel iron-based cellular suicide weapon and its arsenal. We also discuss the importance of ferroptosis in pathophysiology, including the need for a further understanding of the relationship between mitochondria and ferroptosis to identify combinatorial targets that are essential for the development of successful drug discovery.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46655402","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: 5

An emerging probiotic with liver health benefits for smokers 一种对吸烟者有益肝脏健康的新兴益生菌

Life metabolism Pub Date : 2022-11-17 DOI: 10.1093/lifemeta/loac033

W. Jia, Xiaojiao Zheng

引用次数: 0

WTAP: a new player in postnatal BAT development WTAP：产后BAT发展的新玩家

Life metabolism Pub Date : 2022-11-03 DOI: 10.1093/lifemeta/loac031

Sun Lei

引用次数: 0

An atlas of glucose uptake across the entire human body as measured by the total-body PET/CT scanner: a pilot study 全身PET/CT扫描仪测量的整个人体葡萄糖摄取图谱：一项初步研究

Life metabolism Pub Date : 2022-10-27 DOI: 10.1093/lifemeta/loac030

Weizhao Lu, Zhaoping Cheng, Xue Xie, Kun Li, Y. Duan, Min Li, Chao Ma, Sijin Liu, Jianfeng Qiu

{"title":"An atlas of glucose uptake across the entire human body as measured by the total-body PET/CT scanner: a pilot study","authors":"Weizhao Lu, Zhaoping Cheng, Xue Xie, Kun Li, Y. Duan, Min Li, Chao Ma, Sijin Liu, Jianfeng Qiu","doi":"10.1093/lifemeta/loac030","DOIUrl":"https://doi.org/10.1093/lifemeta/loac030","url":null,"abstract":"\u0000 Glucose uptake differs in organs and tissues across the human body. To date, however, there has been no single atlas providing detailed glucose uptake profiles across the entire human body. Therefore, we aimed to generate a detailed profile of glucose uptake across the entire human body using the uEXPLORER positron emission tomography/computed tomography (PET/CT) scanner, which offers the opportunity to collect glucose metabolic imaging quickly and simultaneously in all sites of the body. The standardized uptake value normalized by lean body mass (SUL) of 18F-fluorodeoxyglucose (18F-FDG) was used as a measure of glucose uptake. We developed a fingerprint of glucose uptake reflecting the mean SULs of major organs and parts across the entire human body in 15 healthy-weight and 18 overweight subjects. Using the segmentation of organs and body parts from the atlas, we uncovered the significant impacts of age, sex, and obesity on glucose uptake in organs and parts across the entire body. A difference was recognized between the right and left side of the body. Overall, we generated a total-body glucose uptake atlas that could be used as the reference for the diagnosis and evaluation of disordered states involving dysregulated glucose metabolism.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48938028","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: 2