Life metabolismPub Date : 2023-02-01Epub Date: 2022-08-12DOI: 10.1093/lifemeta/loac016
Juan Wang, Guosheng Liang, Tong-Jin Zhao
{"title":"Adipose triglyceride lipase: the first transacylase for FAHFAs.","authors":"Juan Wang, Guosheng Liang, Tong-Jin Zhao","doi":"10.1093/lifemeta/loac016","DOIUrl":"10.1093/lifemeta/loac016","url":null,"abstract":"<p><p>In a recent article published in <i>Nature</i>, Patel <i>et al</i>. identified adipose triglyceride lipase (ATGL, also known as patatin-like phospholipase domain containing 2) as the first biosynthetic enzyme of fatty acid esters of hydroxy fatty acids (FAHFAs), further expanding the knowledge on bioactive lipid research and being a potential paradigm shift for ATGL studies.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10168671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9446564","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}
Life metabolismPub Date : 2022-12-28eCollection Date: 2022-12-01DOI: 10.1093/lifemeta/loac040
Xin Du, Yisi Hu, Guangping Huang, Fuwen Wei
{"title":"The metabolic adaptation in wild vertebrates via omics approaches.","authors":"Xin Du, Yisi Hu, Guangping Huang, Fuwen Wei","doi":"10.1093/lifemeta/loac040","DOIUrl":"10.1093/lifemeta/loac040","url":null,"abstract":"<p><p>Metabolism is the basis for sustaining life and essential to the adaptive evolution of organisms. With the development of high-throughput sequencing technology, genetic mechanisms of adaptive evolution, including metabolic adaptation, have been extensively resolved by omics approaches, but a deep understanding of genetic and epigenetic metabolic adaptation is still lacking. Exploring metabolic adaptations from genetic and epigenetic perspectives in wild vertebrates is vital to understanding species evolution, especially for the early stages of adaptative evolution. Herein, we summarize the advances in our understanding of metabolic adaptations via omics approaches in wild vertebrates based on three types of cases: extreme environment, periodically changing environment, and changes of species characteristics. We conclude that the understanding of the formation of metabolic adaptations at the genetic level alone can well identify the adaptive genetic variation that has developed during evolution, but cannot resolve the potential impact of metabolic adaptations on the adaptative evolution in the future. Thus, it seems imperative to include epigenomics and metabolomics in the study of adaptation, and that in the future genomic and epigenetic data should be integrated to understand the formation of metabolic adaptation of wild vertebrate organisms.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":" ","pages":"234-241"},"PeriodicalIF":0.0,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47693511","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}
Life metabolismPub Date : 2022-12-17eCollection Date: 2023-04-01DOI: 10.1093/lifemeta/loac039
Liming Wang, Han-Ming Shen
{"title":"TMEM251, a new player in lysosomal enzyme trafficking.","authors":"Liming Wang, Han-Ming Shen","doi":"10.1093/lifemeta/loac039","DOIUrl":"10.1093/lifemeta/loac039","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":" ","pages":"loac039"},"PeriodicalIF":0.0,"publicationDate":"2022-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46930041","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}
Life metabolismPub Date : 2022-12-15eCollection Date: 2022-12-01DOI: 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":"10.1093/lifemeta/loac038","url":null,"abstract":"<p><p>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, i.e. 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.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":" ","pages":"211-223"},"PeriodicalIF":0.0,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45538764","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}
Life metabolismPub Date : 2022-12-09eCollection Date: 2022-12-01DOI: 10.1093/lifemeta/loac037
Yulong Sun, Wenjiao Jiang, Tiffany Horng
{"title":"Circadian metabolism regulates the macrophage inflammatory response.","authors":"Yulong Sun, Wenjiao Jiang, Tiffany Horng","doi":"10.1093/lifemeta/loac037","DOIUrl":"10.1093/lifemeta/loac037","url":null,"abstract":"<p><p>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 suggesting 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.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":" ","pages":"224-233"},"PeriodicalIF":0.0,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44882916","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}
Life metabolismPub Date : 2022-12-01Epub Date: 2022-11-11DOI: 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":"<p><p>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 (<i>K293Q</i><sup><i>flox/flox</i></sup><i>:LysM-cre</i>, 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.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"1 3","pages":"258-269"},"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}
Life metabolismPub Date : 2022-12-01DOI: 10.1093/lifemeta/loac034
Liping Xiang, Xiaoyan Li, Yunchen Luo, Bing Zhou, Yuejun Liu, Yao Li, Duojiao Wu, Lijing Jia, Pei-Wu Zhu, Ming-Hua 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, Ming-Hua Zheng, Hua Wang, Yan Lu","doi":"10.1093/lifemeta/loac034","DOIUrl":"10.1093/lifemeta/loac034","url":null,"abstract":"<p><p>Nonalcoholic steatohepatitis (NASH) has emerged as a major cause of liver failure and hepatocellular carcinoma. Investigation 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.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":" ","pages":"242-257"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44760090","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}
Life metabolismPub Date : 2022-11-25eCollection Date: 2022-10-01DOI: 10.1093/lifemeta/loac035
Jingyi Guo, Yunhao Zhou, Dingfei Liu, Mengfei Wang, Yi Wu, Daolin Tang, Xingguo Liu
{"title":"Mitochondria as multifaceted regulators of ferroptosis.","authors":"Jingyi Guo, Yunhao Zhou, Dingfei Liu, Mengfei Wang, Yi Wu, Daolin Tang, Xingguo Liu","doi":"10.1093/lifemeta/loac035","DOIUrl":"10.1093/lifemeta/loac035","url":null,"abstract":"<p><p>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 mitochondria 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 further understanding of the relationship between mitochondria and ferroptosis to identify combinatorial targets that are essential for the development of successful drug discovery.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":" ","pages":"134-148"},"PeriodicalIF":0.0,"publicationDate":"2022-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46655402","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}
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