Gut microbial co-metabolite 2-methylbutyrylcarnitine exacerbates thrombosis via binding to and activating integrin α2β1
Cell Metab. 2024 Feb 20:S1550-4131(24)00014-7. doi: 10.1016/j.cmet.2024.01.014. Online ahead of print.ABSTRACTThrombosis 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 mic...
Source: Cell Metabolism - February 24, 2024 Category: Cytology Authors: 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 Source Type: research
Methionine secreted by tumor-associated pericytes supports cancer stem cells in clear cell renal carcinoma
Cell Metab. 2024 Feb 13:S1550-4131(24)00018-4. doi: 10.1016/j.cmet.2024.01.018. Online ahead of print.ABSTRACTHere, 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...
Source: Cell Metabolism - February 20, 2024 Category: Cytology Authors: ChuanJie Zhang ZunGuo Du Yi Gao Kiat Shenq Lim WenJie Zhou Hai Huang HongChao He Jun Xiao DanFeng Xu QingQuan Li Source Type: research
IgG is an aging factor that drives adipose tissue fibrosis and metabolic decline
Cell Metab. 2024 Feb 12:S1550-4131(24)00015-9. doi: 10.1016/j.cmet.2024.01.015. Online ahead of print.ABSTRACTAging 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 pro...
Source: Cell Metabolism - February 20, 2024 Category: Cytology 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 Source Type: research
Methionine secreted by tumor-associated pericytes supports cancer stem cells in clear cell renal carcinoma
Cell Metab. 2024 Feb 13:S1550-4131(24)00018-4. doi: 10.1016/j.cmet.2024.01.018. Online ahead of print.ABSTRACTHere, 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...
Source: Cell Metabolism - February 20, 2024 Category: Cytology Authors: ChuanJie Zhang ZunGuo Du Yi Gao Kiat Shenq Lim WenJie Zhou Hai Huang HongChao He Jun Xiao DanFeng Xu QingQuan Li Source Type: research
IgG is an aging factor that drives adipose tissue fibrosis and metabolic decline
Cell Metab. 2024 Feb 12:S1550-4131(24)00015-9. doi: 10.1016/j.cmet.2024.01.015. Online ahead of print.ABSTRACTAging 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 pro...
Source: Cell Metabolism - February 20, 2024 Category: Cytology 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 Source Type: research
Methionine secreted by tumor-associated pericytes supports cancer stem cells in clear cell renal carcinoma
Cell Metab. 2024 Feb 13:S1550-4131(24)00018-4. doi: 10.1016/j.cmet.2024.01.018. Online ahead of print.ABSTRACTHere, 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...
Source: Cell Metabolism - February 20, 2024 Category: Cytology Authors: ChuanJie Zhang ZunGuo Du Yi Gao Kiat Shenq Lim WenJie Zhou Hai Huang HongChao He Jun Xiao DanFeng Xu QingQuan Li Source Type: research
IgG is an aging factor that drives adipose tissue fibrosis and metabolic decline
Cell Metab. 2024 Feb 12:S1550-4131(24)00015-9. doi: 10.1016/j.cmet.2024.01.015. Online ahead of print.ABSTRACTAging 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 pro...
Source: Cell Metabolism - February 20, 2024 Category: Cytology 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 Source Type: research
Sphingolipid metabolism controls mammalian heart regeneration
Cell Metab. 2024 Feb 7:S1550-4131(24)00017-2. doi: 10.1016/j.cmet.2024.01.017. Online ahead of print.ABSTRACTUtilization 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-phosph...
Source: Cell Metabolism - February 17, 2024 Category: Cytology 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 Source Type: research
Sphingolipid metabolism controls mammalian heart regeneration
Cell Metab. 2024 Feb 7:S1550-4131(24)00017-2. doi: 10.1016/j.cmet.2024.01.017. Online ahead of print.ABSTRACTUtilization 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-phosph...
Source: Cell Metabolism - February 17, 2024 Category: Cytology 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 Source Type: research
Sphingolipid metabolism controls mammalian heart regeneration
Cell Metab. 2024 Feb 7:S1550-4131(24)00017-2. doi: 10.1016/j.cmet.2024.01.017. Online ahead of print.ABSTRACTUtilization 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-phosph...
Source: Cell Metabolism - February 17, 2024 Category: Cytology 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 Source Type: research
SLC25A51 decouples the mitochondrial NAD < sup > + < /sup > /NADH ratio to control proliferation of AML cells
Cell Metab. 2024 Feb 13:S1550-4131(24)00013-5. doi: 10.1016/j.cmet.2024.01.013. Online ahead of print.ABSTRACTSLC25A51 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 awa...
Source: Cell Metabolism - February 14, 2024 Category: Cytology Authors: Mu-Jie Lu Jonathan Busquets Valeria Impedovo Crystal N Wilson Hsin-Ru Chan Yu-Tai Chang William Matsui Stefano Tiziani Xiaolu A Cambronne Source Type: research
SLC25A51 decouples the mitochondrial NAD < sup > + < /sup > /NADH ratio to control proliferation of AML cells
Cell Metab. 2024 Feb 13:S1550-4131(24)00013-5. doi: 10.1016/j.cmet.2024.01.013. Online ahead of print.ABSTRACTSLC25A51 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 awa...
Source: Cell Metabolism - February 14, 2024 Category: Cytology Authors: Mu-Jie Lu Jonathan Busquets Valeria Impedovo Crystal N Wilson Hsin-Ru Chan Yu-Tai Chang William Matsui Stefano Tiziani Xiaolu A Cambronne Source Type: research
SLC25A51 decouples the mitochondrial NAD < sup > + < /sup > /NADH ratio to control proliferation of AML cells
Cell Metab. 2024 Feb 13:S1550-4131(24)00013-5. doi: 10.1016/j.cmet.2024.01.013. Online ahead of print.ABSTRACTSLC25A51 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 awa...
Source: Cell Metabolism - February 14, 2024 Category: Cytology Authors: Mu-Jie Lu Jonathan Busquets Valeria Impedovo Crystal N Wilson Hsin-Ru Chan Yu-Tai Chang William Matsui Stefano Tiziani Xiaolu A Cambronne Source Type: research
Dietary elaidic acid boosts tumoral antigen presentation and cancer immunity via ACSL5
Cell Metab. 2024 Feb 8:S1550-4131(24)00012-3. doi: 10.1016/j.cmet.2024.01.012. Online ahead of print.ABSTRACTImmunomodulatory 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 poten...
Source: Cell Metabolism - February 13, 2024 Category: Cytology 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 Source Type: research
DGAT2 inhibition blocks SREBP-1 cleavage and improves hepatic steatosis by increasing phosphatidylethanolamine in the ER
This study reveals a new mechanism that regulates SREBP-1 activation and lipogenesis that is independent of sterols and SREBP-2 in liver.PMID:38340721 | DOI:10.1016/j.cmet.2024.01.011 (Source: Cell Metabolism)
Source: Cell Metabolism - February 10, 2024 Category: Cytology Authors: Shunxing Rong Mingfeng Xia Goncalo Vale Simeng Wang Chai-Wan Kim Shili Li Jeffrey G McDonald Arun Radhakrishnan Jay D Horton Source Type: research
