journal
https://read.qxmd.com/read/38537635/tumor-secreted-fgf21-acts-as-an-immune-suppressor-by-rewiring-cholesterol-metabolism-of-cd8-t-cells
#1
Cegui Hu, Wen Qiao, Xiang Li, Zhi-Kun Ning, Jiang Liu, Sumiya Dalangood, Hanjun Li, Xiang Yu, Zhen Zong, Zhenke Wen, Jun Gui
No abstract text is available yet for this article.
March 26, 2024: Cell Metabolism
https://read.qxmd.com/read/38521058/the-effects-of-pregnancy-its-progression-and-its-cessation-on-human-maternal-biological-aging
#2
LETTER
Hung Pham, Tara Thompson-Felix, Darina Czamara, Jerod M Rasmussen, Adam Lombroso, Sonja Entringer, Elisabeth B Binder, Pathik D Wadhwa, Claudia Buss, Kieran J O'Donnell
No abstract text is available yet for this article.
March 19, 2024: Cell Metabolism
https://read.qxmd.com/read/38513648/cytosolic-ph-is-a-direct-nexus-in-linking-environmental-cues-with-insulin-processing-and-secretion-in-pancreatic-%C3%AE-cells
#3
JOURNAL ARTICLE
Yujiang Fang, Hexi Feng, Bowen Zhang, Shuwei Zhang, Yanjie Zhou, Pengcheng Hao, Zhongshu Zhou, Shanshan Zhou, Nan Li, Yi Hui, Lin Ma, Jie Xiong, Jinjin Wu, Ling Liu, Xiaoqing Zhang
Pancreatic β cells actively respond to glucose fluctuations through regulating insulin processing and secretion. However, how this process is elaborately tuned in circumstance of variable microenvironments as well as β cell-intrinsic states and whether its dysfunction links to metabolic diseases remain largely elusive. Here, we show that the cytosolic pH (pHc) in β cells is increased upon glucose challenge, which can be sensed by Smad5 via its nucleocytoplasmic shuttling. Lesion of Smad5 in β cells results in hyperglycemia and glucose intolerance due to insulin processing and secretion deficiency...
March 15, 2024: Cell Metabolism
https://read.qxmd.com/read/38513649/physiologic-disruption-and-metabolic-reprogramming-in-infection-and-sepsis
#4
REVIEW
Katharina Willmann, Luis F Moita
Effective responses against severe systemic infection require coordination between two complementary defense strategies that minimize the negative impact of infection on the host: resistance, aimed at pathogen elimination, and disease tolerance, which limits tissue damage and preserves organ function. Resistance and disease tolerance mostly rely on divergent metabolic programs that may not operate simultaneously in time and space. Due to evolutionary reasons, the host initially prioritizes the elimination of the pathogen, leading to dominant resistance mechanisms at the potential expense of disease tolerance, which can contribute to organ failure...
March 13, 2024: Cell Metabolism
https://read.qxmd.com/read/38513647/transcriptomic-epigenomic-and-spatial-metabolomic-cell-profiling-redefines-regional-human-kidney-anatomy
#5
JOURNAL ARTICLE
Haikuo Li, Dian Li, Nicolas Ledru, Qiao Xuanyuan, Haojia Wu, Amish Asthana, Lori N Byers, Stefan G Tullius, Giuseppe Orlando, Sushrut S Waikar, Benjamin D Humphreys
A large-scale multimodal atlas that includes major kidney regions is lacking. Here, we employed simultaneous high-throughput single-cell ATAC/RNA sequencing (SHARE-seq) and spatially resolved metabolomics to profile 54 human samples from distinct kidney anatomical regions. We generated transcriptomes of 446,267 cells and chromatin accessibility profiles of 401,875 cells and developed a package to analyze 408,218 spatially resolved metabolomes. We find that the same cell type, including thin limb, thick ascending limb loop of Henle and principal cells, display distinct transcriptomic, chromatin accessibility, and metabolomic signatures, depending on anatomic location...
March 13, 2024: Cell Metabolism
https://read.qxmd.com/read/38490211/acetyl-coa-carboxylase-obstructs-cd8-t%C3%A2-cell-lipid-utilization-in-the-tumor-microenvironment
#6
JOURNAL ARTICLE
Elizabeth G Hunt, Katie E Hurst, Brian P Riesenberg, Andrew S Kennedy, Evelyn J Gandy, Alex M Andrews, Coral Del Mar Alicea Pauneto, Lauren E Ball, Emily D Wallace, Peng Gao, Jeremy Meier, John J Serody, Michael F Coleman, Jessica E Thaxton
The solid tumor microenvironment (TME) imprints a compromised metabolic state in tumor-infiltrating T cells (TILs), hallmarked by the inability to maintain effective energy synthesis for antitumor function and survival. T cells in the TME must catabolize lipids via mitochondrial fatty acid oxidation (FAO) to supply energy in nutrient stress, and it is established that T cells enriched in FAO are adept at cancer control. However, endogenous TILs and unmodified cellular therapy products fail to sustain bioenergetics in tumors...
March 11, 2024: Cell Metabolism
https://read.qxmd.com/read/38490210/judith-campisi-1948-2024
#7
JOURNAL ARTICLE
Eric Verdin
No abstract text is available yet for this article.
March 11, 2024: Cell Metabolism
https://read.qxmd.com/read/38490209/impaired-skeletal-muscle-regeneration-in-diabetes-from-cellular-and-molecular-mechanisms-to-novel-treatments
#8
REVIEW
Ever Espino-Gonzalez, Emilie Dalbram, Rémi Mounier, Julien Gondin, Jean Farup, Niels Jessen, Jonas T Treebak
Diabetes represents a major public health concern with a considerable impact on human life and healthcare expenditures. It is now well established that diabetes is characterized by a severe skeletal muscle pathology that limits functional capacity and quality of life. Increasing evidence indicates that diabetes is also one of the most prevalent disorders characterized by impaired skeletal muscle regeneration, yet underlying mechanisms and therapeutic treatments remain poorly established. In this review, we describe the cellular and molecular alterations currently known to occur during skeletal muscle regeneration in people with diabetes and animal models of diabetes, including its associated comorbidities, e...
March 7, 2024: Cell Metabolism
https://read.qxmd.com/read/38471509/fndc5-is-translated-from-an-upstream-atg-start-codon-and-cleaved-to-produce-irisin-myokine-precursor-protein-in-humans-and-mice
#9
LETTER
Nathan H Witmer, Connor R Linzer, Ryan L Boudreau
Witmer et al. provide genomic and molecular evidence to demonstrate that Fndc5 (irisin myokine precursor protein) is translated in humans from an overlooked upstream ATG codon.
March 6, 2024: Cell Metabolism
https://read.qxmd.com/read/38458203/aging-induced-trna-glu-derived-fragment-impairs-glutamate-biosynthesis-by-targeting-mitochondrial-translation-dependent-cristae-organization
#10
JOURNAL ARTICLE
Dingfeng Li, Xinyi Gao, Xiaolin Ma, Ming Wang, Chuandong Cheng, Tian Xue, Feng Gao, Yong Shen, Juan Zhang, Qiang Liu
Mitochondrial cristae, infoldings of the mitochondrial inner membrane, undergo aberrant changes in their architecture with age. However, the underlying molecular mechanisms and their contribution to brain aging are largely elusive. Here, we observe an age-dependent accumulation of Glu-5'tsRNA-CTC, a transfer-RNA-derived small RNA (tsRNA), derived from nuclear-encoded tRNAGlu in the mitochondria of glutaminergic neurons. Mitochondrial Glu-5'tsRNA-CTC disrupts the binding of mt-tRNALeu and leucyl-tRNA synthetase2 (LaRs2), impairing mt-tRNALeu aminoacylation and mitochondria-encoded protein translation...
March 1, 2024: Cell Metabolism
https://read.qxmd.com/read/38447582/hepatic-malonyl-coa-synthesis-restrains-gluconeogenesis-by-suppressing-fat-oxidation-pyruvate-carboxylation-and-amino-acid-availability
#11
JOURNAL ARTICLE
Stanislaw Deja, Justin A Fletcher, Chai-Wan Kim, Blanka Kucejova, Xiaorong Fu, Monika Mizerska, Morgan Villegas, Natalia Pudelko-Malik, Nicholas Browder, Melissa Inigo-Vollmer, Cameron J Menezes, Prashant Mishra, Eric D Berglund, Jeffrey D Browning, John P Thyfault, Jamey D Young, Jay D Horton, Shawn C Burgess
Acetyl-CoA carboxylase (ACC) promotes prandial liver metabolism by producing malonyl-CoA, a substrate for de novo lipogenesis and an inhibitor of CPT-1-mediated fat oxidation. We report that inhibition of ACC also produces unexpected secondary effects on metabolism. Liver-specific double ACC1/2 knockout (LDKO) or pharmacologic inhibition of ACC increased anaplerosis, tricarboxylic acid (TCA) cycle intermediates, and gluconeogenesis by activating hepatic CPT-1 and pyruvate carboxylase flux in the fed state. Fasting should have marginalized the role of ACC, but LDKO mice maintained elevated TCA cycle intermediates and preserved glycemia during fasting...
March 1, 2024: Cell Metabolism
https://read.qxmd.com/read/38452767/age-related-ciliopathy-obesogenic-shortening-of-melanocortin-4-receptor-bearing-neuronal-primary-cilia
#12
JOURNAL ARTICLE
Manami Oya, Yoshiki Miyasaka, Yoshiko Nakamura, Miyako Tanaka, Takayoshi Suganami, Tomoji Mashimo, Kazuhiro Nakamura
Obesity is often associated with aging. However, the mechanism of age-related obesity is unknown. The melanocortin-4 receptor (MC4R) mediates leptin-melanocortin anti-obesity signaling in the hypothalamus. Here, we discovered that MC4R-bearing primary cilia of hypothalamic neurons progressively shorten with age in rats, correlating with age-dependent metabolic decline and increased adiposity. This "age-related ciliopathy" is promoted by overnutrition-induced upregulation of leptin-melanocortin signaling and inhibited or reversed by dietary restriction or the knockdown of ciliogenesis-associated kinase 1 (CILK1)...
February 27, 2024: Cell Metabolism
https://read.qxmd.com/read/38428435/transforming-the-cardiometabolic-disease-landscape-multimodal-ai-powered-approaches-in-prevention-and-management
#13
REVIEW
Evan D Muse, Eric J Topol
The rise of artificial intelligence (AI) has revolutionized various scientific fields, particularly in medicine, where it has enabled the modeling of complex relationships from massive datasets. Initially, AI algorithms focused on improved interpretation of diagnostic studies such as chest X-rays and electrocardiograms in addition to predicting patient outcomes and future disease onset. However, AI has evolved with the introduction of transformer models, allowing analysis of the diverse, multimodal data sources existing in medicine today...
February 20, 2024: Cell Metabolism
https://read.qxmd.com/read/38401546/gut-microbial-co-metabolite-2-methylbutyrylcarnitine-exacerbates-thrombosis-via-binding-to-and-activating-integrin-%C3%AE-2%C3%AE-1
#14
JOURNAL ARTICLE
Kan Huang, Zilun Li, Xi He, Jun Dai, Bingding Huang, Yongxia Shi, Dongxiao Fan, Zefeng Zhang, Yunchong Liu, Na Li, Zhongyu Zhang, Jiangyun Peng, Chenshu Liu, Renli Zeng, Zhipeng Cen, Tengyao Wang, Wenchao Yang, Meifeng Cen, Jingyu Li, Shuai Yuan, Lu Zhang, Dandan Hu, Shuxiang Huang, Pin Chen, Peilong Lai, Liyan Lin, Jielu Wen, Zhengde Zhao, Xiuyi Huang, Lining Yuan, Lifang Zhou, Haoliang Wu, Lihua Huang, Kai Feng, Jian Wang, Baolin Liao, Weiping Cai, Xilong Deng, Yueping Li, Jianping Li, Zhongwei Hu, Li Yang, Jiaojiao Li, Youguang Zhuo, Fuchun Zhang, Lin Lin, Yifeng Luo, Wei Zhang, Qianlin Ni, Xiqiang Hong, Guangqi Chang, Yang Zhang, Dongxian Guan, Weikang Cai, Yutong Lu, Fang Li, Li Yan, Meng Ren, Linghua Li, Sifan Chen
Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice...
February 20, 2024: Cell Metabolism
https://read.qxmd.com/read/38378000/methionine-secreted-by-tumor-associated-pericytes-supports-cancer-stem-cells-in-clear-cell-renal-carcinoma
#15
JOURNAL ARTICLE
ChuanJie Zhang, ZunGuo Du, Yi Gao, Kiat Shenq Lim, WenJie Zhou, Hai Huang, HongChao He, Jun Xiao, DanFeng Xu, QingQuan Li
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...
February 13, 2024: Cell Metabolism
https://read.qxmd.com/read/38354740/slc25a51-decouples-the-mitochondrial-nad-nadh-ratio-to-control-proliferation-of-aml-cells
#16
JOURNAL ARTICLE
Mu-Jie Lu, Jonathan Busquets, Valeria Impedovo, Crystal N Wilson, Hsin-Ru Chan, Yu-Tai Chang, William Matsui, Stefano Tiziani, Xiaolu A Cambronne
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...
February 13, 2024: Cell Metabolism
https://read.qxmd.com/read/38378001/igg-is-an-aging-factor-that-drives-adipose-tissue-fibrosis-and-metabolic-decline
#17
JOURNAL ARTICLE
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
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...
February 12, 2024: Cell Metabolism
https://read.qxmd.com/read/38350448/dietary-elaidic-acid-boosts-tumoral-antigen-presentation-and-cancer-immunity-via-acsl5
#18
JOURNAL ARTICLE
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
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...
February 8, 2024: Cell Metabolism
https://read.qxmd.com/read/38367623/sphingolipid-metabolism-controls-mammalian-heart-regeneration
#19
JOURNAL ARTICLE
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
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...
February 7, 2024: Cell Metabolism
https://read.qxmd.com/read/38340721/dgat2-inhibition-blocks-srebp-1-cleavage-and-improves-hepatic-steatosis-by-increasing-phosphatidylethanolamine-in-the-er
#20
JOURNAL ARTICLE
Shunxing Rong, Mingfeng Xia, Goncalo Vale, Simeng Wang, Chai-Wan Kim, Shili Li, Jeffrey G McDonald, Arun Radhakrishnan, Jay D Horton
Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step of triglyceride (TG) synthesis. DGAT2 deletion in mice lowers liver TGs, and DGAT2 inhibitors are under investigation for the treatment of fatty liver disease. Here, we show that DGAT2 inhibition also suppressed SREBP-1 cleavage, reduced fatty acid synthesis, and lowered TG accumulation and secretion from liver. DGAT2 inhibition increased phosphatidylethanolamine (PE) levels in the endoplasmic reticulum (ER) and inhibited SREBP-1 cleavage, while DGAT2 overexpression lowered ER PE concentrations and increased SREBP-1 cleavage in vivo...
February 1, 2024: Cell Metabolism
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