Cell metabolism最新文献_第3页

IgG is an aging factor that drives adipose tissue fibrosis and metabolic decline. IgG 是促使脂肪组织纤维化和代谢衰退的衰老因子。

Cell metabolism Pub Date : 2024-04-02 Epub Date: 2024-02-19 DOI: 10.1016/j.cmet.2024.01.015

Lexiang Yu, Qianfen Wan, Qiongming Liu, Yong Fan, Qiuzhong Zhou, Alicja A Skowronski, Summer Wang, Zhengping Shao, Chen-Yu Liao, Lei Ding, Brian K Kennedy, Shan Zha, Jianwen Que, Charles A LeDuc, Lei Sun, Liheng Wang, Li Qiang

{"title":"IgG is an aging factor that drives adipose tissue fibrosis and metabolic decline.","authors":"Lexiang Yu, Qianfen Wan, Qiongming Liu, Yong Fan, Qiuzhong Zhou, Alicja A Skowronski, Summer Wang, Zhengping Shao, Chen-Yu Liao, Lei Ding, Brian K Kennedy, Shan Zha, Jianwen Que, Charles A LeDuc, Lei Sun, Liheng Wang, Li Qiang","doi":"10.1016/j.cmet.2024.01.015","DOIUrl":"10.1016/j.cmet.2024.01.015","url":null,"abstract":"Aging is underpinned by pronounced metabolic decline; however, the drivers remain obscure. Here, we report that IgG accumulates during aging, particularly in white adipose tissue (WAT), to impair adipose tissue function and metabolic health. Caloric restriction (CR) decreases IgG accumulation in WAT, whereas replenishing IgG counteracts CR's metabolic benefits. IgG activates macrophages via Ras signaling and consequently induces fibrosis in WAT through the TGF-β/SMAD pathway. Consistently, B cell null mice are protected from aging-associated WAT fibrosis, inflammation, and insulin resistance, unless exposed to IgG. Conditional ablation of the IgG recycling receptor, neonatal Fc receptor (FcRn), in macrophages prevents IgG accumulation in aging, resulting in prolonged healthspan and lifespan. Further, targeting FcRn by antisense oligonucleotide restores WAT integrity and metabolic health in aged mice. These findings pinpoint IgG as a hidden culprit in aging and enlighten a novel strategy to rejuvenate metabolic health.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"793-807.e5"},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11070064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139914255","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

Dietary elaidic acid boosts tumoral antigen presentation and cancer immunity via ACSL5. 膳食中的麦饭石酸可通过 ACSL5 促进肿瘤抗原呈递和癌症免疫。

Cell metabolism Pub Date : 2024-04-02 Epub Date: 2024-02-12 DOI: 10.1016/j.cmet.2024.01.012

Yongfeng Lai, Yuan Gao, Junhong Lin, Fangfang Liu, Liguo Yang, Jie Zhou, Ying Xue, Yan Li, Zhenzhen Chang, Jing Li, Tengfei Chao, Jing Chen, Xiang Cheng, Xianfu Gao, Xiong Li, Fujia Lu, Qian Chu, Weimin Wang

{"title":"Dietary elaidic acid boosts tumoral antigen presentation and cancer immunity via ACSL5.","authors":"Yongfeng Lai, Yuan Gao, Junhong Lin, Fangfang Liu, Liguo Yang, Jie Zhou, Ying Xue, Yan Li, Zhenzhen Chang, Jing Li, Tengfei Chao, Jing Chen, Xiang Cheng, Xianfu Gao, Xiong Li, Fujia Lu, Qian Chu, Weimin Wang","doi":"10.1016/j.cmet.2024.01.012","DOIUrl":"10.1016/j.cmet.2024.01.012","url":null,"abstract":"Immunomodulatory effects of long-chain fatty acids (LCFAs) and their activating enzyme, acyl-coenzyme A (CoA) synthetase long-chain family (ACSL), in the tumor microenvironment remain largely unknown. Here, we find that ACSL5 functions as an immune-dependent tumor suppressor. ACSL5 expression sensitizes tumors to PD-1 blockade therapy in vivo and the cytotoxicity mediated by CD8+ T cells in vitro via regulation of major histocompatibility complex class I (MHC-I)-mediated antigen presentation. Through screening potential substrates for ACSL5, we further identify that elaidic acid (EA), a trans LCFA that has long been considered harmful to human health, phenocopies to enhance MHC-I expression. EA supplementation can suppress tumor growth and sensitize PD-1 blockade therapy. Clinically, ACSL5 expression is positively associated with improved survival in patients with lung cancer, and plasma EA level is also predictive for immunotherapy efficiency. Our findings provide a foundation for enhancing immunotherapy through either targeting ACSL5 or metabolic reprogramming of antigen presentation via dietary EA supplementation.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"822-838.e8"},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139731232","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

SLC25A51 decouples the mitochondrial NAD⁺/NADH ratio to control proliferation of AML cells. SLC25A51 可使线粒体 NAD+/NADH 比率脱钩，从而控制 AML 细胞的增殖。

Cell metabolism Pub Date : 2024-04-02 Epub Date: 2024-02-14 DOI: 10.1016/j.cmet.2024.01.013

Mu-Jie Lu, Jonathan Busquets, Valeria Impedovo, Crystal N Wilson, Hsin-Ru Chan, Yu-Tai Chang, William Matsui, Stefano Tiziani, Xiaolu A Cambronne

{"title":"SLC25A51 decouples the mitochondrial NAD+/NADH ratio to control proliferation of AML cells.","authors":"Mu-Jie Lu, Jonathan Busquets, Valeria Impedovo, Crystal N Wilson, Hsin-Ru Chan, Yu-Tai Chang, William Matsui, Stefano Tiziani, Xiaolu A Cambronne","doi":"10.1016/j.cmet.2024.01.013","DOIUrl":"10.1016/j.cmet.2024.01.013","url":null,"abstract":"SLC25A51 selectively imports oxidized NAD+ into the mitochondrial matrix and is required for sustaining cell respiration. We observed elevated expression of SLC25A51 that correlated with poorer outcomes in patients with acute myeloid leukemia (AML), and we sought to determine the role SLC25A51 may serve in this disease. We found that lowering SLC25A51 levels led to increased apoptosis and prolonged survival in orthotopic xenograft models. Metabolic flux analyses indicated that depletion of SLC25A51 shunted flux away from mitochondrial oxidative pathways, notably without increased glycolytic flux. Depletion of SLC25A51 combined with 5-azacytidine treatment limits expansion of AML cells in vivo. Together, the data indicate that AML cells upregulate SLC25A51 to decouple mitochondrial NAD+/NADH for a proliferative advantage by supporting oxidative reactions from a variety of fuels. Thus, SLC25A51 represents a critical regulator that can be exploited by cancer cells and may be a vulnerability for refractory AML.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"808-821.e6"},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10990793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736898","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

Methionine secreted by tumor-associated pericytes supports cancer stem cells in clear cell renal carcinoma. 肿瘤相关周细胞分泌的蛋氨酸支持透明细胞肾癌中的癌症干细胞。

Cell metabolism Pub Date : 2024-04-02 Epub Date: 2024-02-19 DOI: 10.1016/j.cmet.2024.01.018

ChuanJie Zhang, ZunGuo Du, Yi Gao, Kiat Shenq Lim, WenJie Zhou, Hai Huang, HongChao He, Jun Xiao, DanFeng Xu, QingQuan Li

{"title":"Methionine secreted by tumor-associated pericytes supports cancer stem cells in clear cell renal carcinoma.","authors":"ChuanJie Zhang, ZunGuo Du, Yi Gao, Kiat Shenq Lim, WenJie Zhou, Hai Huang, HongChao He, Jun Xiao, DanFeng Xu, QingQuan Li","doi":"10.1016/j.cmet.2024.01.018","DOIUrl":"10.1016/j.cmet.2024.01.018","url":null,"abstract":"Here, we identify a subset of vascular pericytes, defined by expression of platelet-derived growth factor receptor beta (PDGFR-β) and G-protein-coupled receptor 91 (GPR91), that promote tumorigenesis and tyrosine kinase inhibitors (TKIs) resistance by functioning as the primary methionine source for cancer stem cells (CSCs) in clear cell renal cell carcinoma (ccRCC). Tumor-cell-derived succinate binds to GPR91 on pericyte to activate autophagy for methionine production. CSCs use methionine to create stabilizing N6-methyladenosine in ATPase-family-AAA-domain-containing 2 (ATAD2) mRNA, and the resulting ATAD2 protein complexes with SRY-box transcription factor 9 to assemble super enhancers and thereby dictate its target genes that feature prominently in CSCs. Targeting PDGFR-β+GPR91+ pericytes with specific GRP91 antagonists reduce intratumoral methionine level, eliminate CSCs, and enhance TKIs sensitivity. These results unraveled the mechanisms by which PDGFR-β+GPR91+ pericytes provide supportive niche for CSCs and could be used to develop targets for treating ccRCC.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"778-792.e10"},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139914256","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

Sphingolipid metabolism controls mammalian heart regeneration. 鞘脂代谢控制着哺乳动物心脏的再生。

Cell metabolism Pub Date : 2024-04-02 Epub Date: 2024-02-16 DOI: 10.1016/j.cmet.2024.01.017

Xiaoqian Ji, Zihao Chen, Qiyuan Wang, Bin Li, Yan Wei, Yun Li, Jianqing Lin, Weisheng Cheng, Yijie Guo, Shilin Wu, Longkun Mao, Yuzhou Xiang, Tian Lan, Shanshan Gu, Meng Wei, Joe Z Zhang, Lan Jiang, Jia Wang, Jin Xu, Nan Cao

{"title":"Sphingolipid metabolism controls mammalian heart regeneration.","authors":"Xiaoqian Ji, Zihao Chen, Qiyuan Wang, Bin Li, Yan Wei, Yun Li, Jianqing Lin, Weisheng Cheng, Yijie Guo, Shilin Wu, Longkun Mao, Yuzhou Xiang, Tian Lan, Shanshan Gu, Meng Wei, Joe Z Zhang, Lan Jiang, Jia Wang, Jin Xu, Nan Cao","doi":"10.1016/j.cmet.2024.01.017","DOIUrl":"10.1016/j.cmet.2024.01.017","url":null,"abstract":"Utilization of lipids as energy substrates after birth causes cardiomyocyte (CM) cell-cycle arrest and loss of regenerative capacity in mammalian hearts. Beyond energy provision, proper management of lipid composition is crucial for cellular and organismal health, but its role in heart regeneration remains unclear. Here, we demonstrate widespread sphingolipid metabolism remodeling in neonatal hearts after injury and find that SphK1 and SphK2, isoenzymes producing the same sphingolipid metabolite sphingosine-1-phosphate (S1P), differently regulate cardiac regeneration. SphK2 is downregulated during heart development and determines CM proliferation via nuclear S1P-dependent modulation of histone acetylation. Reactivation of SphK2 induces adult CM cell-cycle re-entry and cytokinesis, thereby enhancing regeneration. Conversely, SphK1 is upregulated during development and promotes fibrosis through an S1P autocrine mechanism in cardiac fibroblasts. By fine-tuning the activity of each SphK isoform, we develop a therapy that simultaneously promotes myocardial repair and restricts fibrotic scarring to regenerate the infarcted adult hearts.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"839-856.e8"},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898376","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

Interorgan rhythmicity as a feature of healthful metabolism. 器官间节律性是健康新陈代谢的一个特征。

Cell metabolism Pub Date : 2024-04-02 Epub Date: 2024-02-08 DOI: 10.1016/j.cmet.2024.01.009

Joseph Bass

引用次数: 0

Transforming the cardiometabolic disease landscape: Multimodal AI-powered approaches in prevention and management. 改变心脏代谢疾病的格局：人工智能驱动的多模式预防和管理方法。

Cell metabolism Pub Date : 2024-04-02 Epub Date: 2024-02-29 DOI: 10.1016/j.cmet.2024.02.002

Evan D Muse, Eric J Topol

引用次数: 0

Judith Campisi (1948-2024). 朱迪斯-坎皮西（1948-2024）。

Cell metabolism Pub Date : 2024-04-02 Epub Date: 2024-03-14 DOI: 10.1016/j.cmet.2024.03.001

Eric Verdin

引用次数: 0

Itaconate boosts malaria via induction of PD-L1. 伊塔康酸通过诱导 PD-L1 促进疟疾的发生。

Cell metabolism Pub Date : 2024-03-05 DOI: 10.1016/j.cmet.2024.02.005

Yukun Min, Luke A J O'Neill

引用次数: 0

Psychological stress-induced microbial metabolite indole-3-acetate disrupts intestinal cell lineage commitment. 心理压力诱导的微生物代谢物吲哚-3-乙酸酯会扰乱肠细胞系的形成。

Cell metabolism Pub Date : 2024-03-05 Epub Date: 2024-01-23 DOI: 10.1016/j.cmet.2023.12.026

Wei Wei, Yali Liu, Yuanlong Hou, Shuqi Cao, Zhuo Chen, Youying Zhang, Xiaoying Cai, Qingyuan Yan, Ziguang Li, Yonggui Yuan, Guangji Wang, Xiao Zheng, Haiping Hao

{"title":"Psychological stress-induced microbial metabolite indole-3-acetate disrupts intestinal cell lineage commitment.","authors":"Wei Wei, Yali Liu, Yuanlong Hou, Shuqi Cao, Zhuo Chen, Youying Zhang, Xiaoying Cai, Qingyuan Yan, Ziguang Li, Yonggui Yuan, Guangji Wang, Xiao Zheng, Haiping Hao","doi":"10.1016/j.cmet.2023.12.026","DOIUrl":"10.1016/j.cmet.2023.12.026","url":null,"abstract":"The brain and gut are intricately connected and respond to various stimuli. Stress-induced brain-gut communication is implicated in the pathogenesis and relapse of gut disorders. The mechanism that relays psychological stress to the intestinal epithelium, resulting in maladaptation, remains poorly understood. Here, we describe a stress-responsive brain-to-gut metabolic axis that impairs intestinal stem cell (ISC) lineage commitment. Psychological stress-triggered sympathetic output enriches gut commensal Lactobacillus murinus, increasing the production of indole-3-acetate (IAA), which contributes to a transferrable loss of intestinal secretory cells. Bacterial IAA disrupts ISC mitochondrial bioenergetics and thereby prevents secretory lineage commitment in a cell-intrinsic manner. Oral α-ketoglutarate supplementation bolsters ISC differentiation and confers resilience to stress-triggered intestinal epithelial injury. We confirm that fecal IAA is higher in patients with mental distress and is correlated with gut dysfunction. These findings uncover a microbe-mediated brain-gut pathway that could be therapeutically targeted for stress-driven gut-brain comorbidities.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"466-483.e7"},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547913","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