Microglial lipid droplet accumulation in tauopathy brain is regulated by neuronal AMPK
Cell Metab. 2024 Apr 16:S1550-4131(24)00118-9. doi: 10.1016/j.cmet.2024.03.014. Online ahead of print.ABSTRACTThe accumulation of lipid droplets (LDs) in aging and Alzheimer's disease brains is considered a pathological phenomenon with unresolved cellular and molecular mechanisms. Utilizing stimulated Raman scattering (SRS) microscopy, we observed significant in situ LD accumulation in microglia of tauopathy mouse brains. SRS imaging, combined with deuterium oxide (D2O) labeling, revealed heightened lipogenesis and impaired lipid turnover within LDs in tauopathy fly brains and human neurons derived from induced pluripotent...
Source: Cell Metabolism - April 24, 2024 Category: Cytology Authors: Yajuan Li Daniel Munoz-Mayorga Yuhang Nie Ningxin Kang Yuren Tao Jessica Lagerwall Carla Pernaci Genevieve Curtin Nicole G Coufal Jerome Mertens Lingyan Shi Xu Chen Source Type: research
Microglial lipid droplet accumulation in tauopathy brain is regulated by neuronal AMPK
Cell Metab. 2024 Apr 16:S1550-4131(24)00118-9. doi: 10.1016/j.cmet.2024.03.014. Online ahead of print.ABSTRACTThe accumulation of lipid droplets (LDs) in aging and Alzheimer's disease brains is considered a pathological phenomenon with unresolved cellular and molecular mechanisms. Utilizing stimulated Raman scattering (SRS) microscopy, we observed significant in situ LD accumulation in microglia of tauopathy mouse brains. SRS imaging, combined with deuterium oxide (D2O) labeling, revealed heightened lipogenesis and impaired lipid turnover within LDs in tauopathy fly brains and human neurons derived from induced pluripotent...
Source: Cell Metabolism - April 24, 2024 Category: Cytology Authors: Yajuan Li Daniel Munoz-Mayorga Yuhang Nie Ningxin Kang Yuren Tao Jessica Lagerwall Carla Pernaci Genevieve Curtin Nicole G Coufal Jerome Mertens Lingyan Shi Xu Chen Source Type: research
Loss of GPR75 protects against non-alcoholic fatty liver disease and body fat accumulation
This study investigated the role of adiposity-associated orphan G protein-coupled receptor 75 (GPR75) in liver lipid accumulation. We profiled Gpr75 expression and report that it is most abundant in the brain. Next, we generated the first single-cell-level analysis of Gpr75 and identified a subpopulation co-expressed with key appetite-regulating hypothalamic neurons. CRISPR-Cas9-deleted Gpr75 mice fed a palatable western diet high in fat adjusted caloric intake to remain in energy balance, thereby preventing NAFLD. Consistent with mouse results, analysis of whole-exome sequencing data from 428,719 individuals (UK Biobank) ...
Source: Cell Metabolism - April 23, 2024 Category: Cytology Authors: Alasdair Leeson-Payne Jean Iyinikkel Cameron Malcolm Brian Y H Lam Nadine Sommer Georgina K C Dowsett Pablo B Martinez de Morentin Dawn Thompson Alasdair Mackenzie Raffaella Chianese Katherine Kentistou Eugene J Gardner John R B Perry Felix Grassmann John Source Type: research
QDPR deficiency drives immune suppression in pancreatic cancer
Cell Metab. 2024 Apr 15:S1550-4131(24)00119-0. doi: 10.1016/j.cmet.2024.03.015. Online ahead of print.ABSTRACTThe relevance of biopterin metabolism in resistance to immune checkpoint blockade (ICB) therapy remains unknown. We demonstrate that the deficiency of quinoid dihydropteridine reductase (QDPR), a critical enzyme regulating biopterin metabolism, causes metabolite dihydrobiopterin (BH2) accumulation and decreases the ratio of tetrahydrobiopterin (BH4) to BH2 in pancreatic ductal adenocarcinomas (PDACs). The reduced BH4/BH2 ratio leads to an increase in reactive oxygen species (ROS) generation and a decrease in the di...
Source: Cell Metabolism - April 20, 2024 Category: Cytology Authors: Ji Liu Xiaowei He Shuang Deng Sihan Zhao Shaoping Zhang Ziming Chen Chunling Xue Lingxing Zeng Hongzhe Zhao Yifan Zhou Ruihong Bai Zilan Xu Shaoqiu Liu Quanbo Zhou Mei Li Jialiang Zhang Xudong Huang Rufu Chen Liqin Wang Dongxin Lin Jian Zheng Source Type: research
QDPR deficiency drives immune suppression in pancreatic cancer
Cell Metab. 2024 Apr 15:S1550-4131(24)00119-0. doi: 10.1016/j.cmet.2024.03.015. Online ahead of print.ABSTRACTThe relevance of biopterin metabolism in resistance to immune checkpoint blockade (ICB) therapy remains unknown. We demonstrate that the deficiency of quinoid dihydropteridine reductase (QDPR), a critical enzyme regulating biopterin metabolism, causes metabolite dihydrobiopterin (BH2) accumulation and decreases the ratio of tetrahydrobiopterin (BH4) to BH2 in pancreatic ductal adenocarcinomas (PDACs). The reduced BH4/BH2 ratio leads to an increase in reactive oxygen species (ROS) generation and a decrease in the di...
Source: Cell Metabolism - April 20, 2024 Category: Cytology Authors: Ji Liu Xiaowei He Shuang Deng Sihan Zhao Shaoping Zhang Ziming Chen Chunling Xue Lingxing Zeng Hongzhe Zhao Yifan Zhou Ruihong Bai Zilan Xu Shaoqiu Liu Quanbo Zhou Mei Li Jialiang Zhang Xudong Huang Rufu Chen Liqin Wang Dongxin Lin Jian Zheng Source Type: research
The intersection of frailty and metabolism
Cell Metab. 2024 Apr 5:S1550-4131(24)00091-3. doi: 10.1016/j.cmet.2024.03.012. Online ahead of print.ABSTRACTOn average, aging is associated with unfavorable changes in cellular metabolism, which are the processes involved in the storage and expenditure of energy. However, metabolic dysregulation may not occur to the same extent in all older individuals as people age at different rates. Those who are aging rapidly are at increased risk of adverse health outcomes and are said to be "frail." Here, we explore the links between frailty and metabolism, including metabolic contributors and consequences of frailty. We examine how...
Source: Cell Metabolism - April 13, 2024 Category: Cytology Authors: Manish Mishra Judy Wu Alice E Kane Susan E Howlett Source Type: research
The intersection of frailty and metabolism
Cell Metab. 2024 Apr 5:S1550-4131(24)00091-3. doi: 10.1016/j.cmet.2024.03.012. Online ahead of print.ABSTRACTOn average, aging is associated with unfavorable changes in cellular metabolism, which are the processes involved in the storage and expenditure of energy. However, metabolic dysregulation may not occur to the same extent in all older individuals as people age at different rates. Those who are aging rapidly are at increased risk of adverse health outcomes and are said to be "frail." Here, we explore the links between frailty and metabolism, including metabolic contributors and consequences of frailty. We examine how...
Source: Cell Metabolism - April 13, 2024 Category: Cytology Authors: Manish Mishra Judy Wu Alice E Kane Susan E Howlett Source Type: research
The intersection of frailty and metabolism
Cell Metab. 2024 Apr 5:S1550-4131(24)00091-3. doi: 10.1016/j.cmet.2024.03.012. Online ahead of print.ABSTRACTOn average, aging is associated with unfavorable changes in cellular metabolism, which are the processes involved in the storage and expenditure of energy. However, metabolic dysregulation may not occur to the same extent in all older individuals as people age at different rates. Those who are aging rapidly are at increased risk of adverse health outcomes and are said to be "frail." Here, we explore the links between frailty and metabolism, including metabolic contributors and consequences of frailty. We examine how...
Source: Cell Metabolism - April 13, 2024 Category: Cytology Authors: Manish Mishra Judy Wu Alice E Kane Susan E Howlett Source Type: research
The intersection of frailty and metabolism
Cell Metab. 2024 Apr 5:S1550-4131(24)00091-3. doi: 10.1016/j.cmet.2024.03.012. Online ahead of print.ABSTRACTOn average, aging is associated with unfavorable changes in cellular metabolism, which are the processes involved in the storage and expenditure of energy. However, metabolic dysregulation may not occur to the same extent in all older individuals as people age at different rates. Those who are aging rapidly are at increased risk of adverse health outcomes and are said to be "frail." Here, we explore the links between frailty and metabolism, including metabolic contributors and consequences of frailty. We examine how...
Source: Cell Metabolism - April 13, 2024 Category: Cytology Authors: Manish Mishra Judy Wu Alice E Kane Susan E Howlett Source Type: research
New and emerging treatments for metabolic dysfunction-associated steatohepatitis
Cell Metab. 2024 Apr 7:S1550-4131(24)00090-1. doi: 10.1016/j.cmet.2024.03.011. Online ahead of print.ABSTRACTMetabolic dysfunction-associated steatohepatitis (MASH) is a leading etiology of chronic liver disease worldwide, with increasing incidence and prevalence in the setting of the obesity epidemic. MASH is also a leading indication for liver transplantation, given its associated risk of progression to end-stage liver disease. A key challenge in managing MASH is the lack of approved pharmacotherapy. In its absence, lifestyle interventions with a focus on healthy nutrition and regular physical activity have been the corn...
Source: Cell Metabolism - April 12, 2024 Category: Cytology Authors: Monica A Tincopa Quentin M Anstee Rohit Loomba Source Type: research
New and emerging treatments for metabolic dysfunction-associated steatohepatitis
Cell Metab. 2024 Apr 7:S1550-4131(24)00090-1. doi: 10.1016/j.cmet.2024.03.011. Online ahead of print.ABSTRACTMetabolic dysfunction-associated steatohepatitis (MASH) is a leading etiology of chronic liver disease worldwide, with increasing incidence and prevalence in the setting of the obesity epidemic. MASH is also a leading indication for liver transplantation, given its associated risk of progression to end-stage liver disease. A key challenge in managing MASH is the lack of approved pharmacotherapy. In its absence, lifestyle interventions with a focus on healthy nutrition and regular physical activity have been the corn...
Source: Cell Metabolism - April 12, 2024 Category: Cytology Authors: Monica A Tincopa Quentin M Anstee Rohit Loomba Source Type: research
ATF3 and CH25H regulate effector trogocytosis and anti-tumor activities of endogenous and immunotherapeutic cytotoxic T lymphocytes
Cell Metab. 2024 Apr 10:S1550-4131(24)00122-0. doi: 10.1016/j.cmet.2024.04.002. Online ahead of print.NO ABSTRACTPMID:38604169 | DOI:10.1016/j.cmet.2024.04.002 (Source: Cell Metabolism)
Source: Cell Metabolism - April 11, 2024 Category: Cytology Authors: Zhen Lu Noreen McBrearty Jinyun Chen Vivek S Tomar Hongru Zhang Gianluca De Rosa Aiwen Tan Aalim M Weljie Daniel P Beiting Zhen Miao Subin S George Allison Berger Gurpanna Saggu J Alan Diehl Constantinos Koumenis Serge Y Fuchs Source Type: research
Single-cell senescence identification reveals senescence heterogeneity, trajectory, and modulators
We present here a machine learning program senescent cell identification (SenCID), which accurately identifies senescent cells in both bulk and single-cell transcriptome. Trained on 602 samples from 52 senescence transcriptome datasets spanning 30 cell types, SenCID identifies six major senescence identities (SIDs). Different SIDs exhibit different senescence baselines, stemness, gene functions, and responses to senolytics. SenCID enables the reconstruction of senescent trajectories under normal aging, chronic diseases, and COVID-19. Additionally, when applied to single-cell Perturb-seq data, SenCID helps reveal a hierarch...
Source: Cell Metabolism - April 11, 2024 Category: Cytology Authors: Wanyu Tao Zhengqing Yu Jing-Dong J Han Source Type: research
ATF3 and CH25H regulate effector trogocytosis and anti-tumor activities of endogenous and immunotherapeutic cytotoxic T lymphocytes
Cell Metab. 2024 Apr 10:S1550-4131(24)00122-0. doi: 10.1016/j.cmet.2024.04.002. Online ahead of print.NO ABSTRACTPMID:38604169 | DOI:10.1016/j.cmet.2024.04.002 (Source: Cell Metabolism)
Source: Cell Metabolism - April 11, 2024 Category: Cytology Authors: Zhen Lu Noreen McBrearty Jinyun Chen Vivek S Tomar Hongru Zhang Gianluca De Rosa Aiwen Tan Aalim M Weljie Daniel P Beiting Zhen Miao Subin S George Allison Berger Gurpanna Saggu J Alan Diehl Constantinos Koumenis Serge Y Fuchs Source Type: research
Single-cell senescence identification reveals senescence heterogeneity, trajectory, and modulators
We present here a machine learning program senescent cell identification (SenCID), which accurately identifies senescent cells in both bulk and single-cell transcriptome. Trained on 602 samples from 52 senescence transcriptome datasets spanning 30 cell types, SenCID identifies six major senescence identities (SIDs). Different SIDs exhibit different senescence baselines, stemness, gene functions, and responses to senolytics. SenCID enables the reconstruction of senescent trajectories under normal aging, chronic diseases, and COVID-19. Additionally, when applied to single-cell Perturb-seq data, SenCID helps reveal a hierarch...
Source: Cell Metabolism - April 11, 2024 Category: Cytology Authors: Wanyu Tao Zhengqing Yu Jing-Dong J Han Source Type: research
