Cell metabolism最新文献_第3页

GPR56: GPCR as a guardian against ferroptosis GPR56：GPCR 是防止铁变态反应的卫士

IF 29 1区生物学

Cell metabolism Pub Date : 2024-11-05 DOI: 10.1016/j.cmet.2024.08.011

Yuelong Yan, Li Zhuang, Boyi Gan

引用次数: 0

A sympathetic paradigm shift for the role of NPY in obesity NPY 在肥胖症中作用的同情范式转变

IF 29 1区生物学

Cell metabolism Pub Date : 2024-11-05 DOI: 10.1016/j.cmet.2024.10.010

Olivier Lavoie, Alexandre Caron

引用次数: 0

Non-invasive lipid panel of MASLD fibrosis transition underscores the role of lipoprotein sulfatides in hepatic immunomodulation MASLD纤维化转变的非侵入性脂质面板强调了脂蛋白硫化物在肝脏免疫调节中的作用

IF 29 1区生物学

Cell metabolism Pub Date : 2024-11-04 DOI: 10.1016/j.cmet.2024.09.009

Sin Man Lam, Zehua Wang, Jin-Wen Song, Yue Shi, Wen-Yue Liu, Lin-Yu Wan, Kaibo Duan, Gek Huey Chua, Yingjuan Zhou, Guibin Wang, Xiahe Huang, Yingchun Wang, Fu-Sheng Wang, Ming-Hua Zheng, Guanghou Shui

{"title":"Non-invasive lipid panel of MASLD fibrosis transition underscores the role of lipoprotein sulfatides in hepatic immunomodulation","authors":"Sin Man Lam, Zehua Wang, Jin-Wen Song, Yue Shi, Wen-Yue Liu, Lin-Yu Wan, Kaibo Duan, Gek Huey Chua, Yingjuan Zhou, Guibin Wang, Xiahe Huang, Yingchun Wang, Fu-Sheng Wang, Ming-Hua Zheng, Guanghou Shui","doi":"10.1016/j.cmet.2024.09.009","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.09.009","url":null,"abstract":"There exists a pressing need for a non-invasive panel that differentiates mild fibrosis from non-fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). In this work, we applied quantitative lipidomics and sterolomics on sera from the PERSONS cohort with biopsy-based histological assessment of liver pathology. We trained a lasso regression model using quantitative omics data and clinical variables, deriving a combinatorial panel of lipids and clinical indices that differentiates mild fibrosis (>F1, n = 324) from non-fibrosis (F0, n = 195), with an area under receiver operating characteristic curve (AUROC) at 0.775 (95% confidence interval [CI]: 0.735–0.816). Circulating sulfatides (SLs) emerged as central lipids distinctly associated with fibrosis pathogenesis in MASLD. Lipidomics analysis of lipoprotein fractions revealed a redistribution of circulating SLs from high-density lipoproteins (HDLs) onto low-density lipoproteins (LDLs) in MASLD fibrosis. We further verified that patient LDLs with reduced SL content triggered a smaller activation of type II natural killer T lymphocytes, compared with control LDLs. Our results suggest that hepatic crosstalk with systemic immunity mediated by lipoprotein metabolism underlies fibrosis progression at early-stage MASLD.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"18 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A blood-based biomarker panel for non-invasive diagnosis of metabolic dysfunction-associated steatohepatitis 用于无创诊断代谢功能障碍相关性脂肪性肝炎的血液生物标记物面板

IF 29 1区生物学

Cell metabolism Pub Date : 2024-11-04 DOI: 10.1016/j.cmet.2024.10.008

Xiang Zhang, Ming-Hua Zheng, Dehua Liu, Yufeng Lin, Sherlot Juan Song, Eagle Siu-Hong Chu, Dabin Liu, Seema Singh, Michael Berman, Harry Cheuk-Hay Lau, Hongyan Gou, Grace Lai-Hung Wong, Ni Zhang, Hai-Yang Yuan, Rohit Loomba, Vincent Wai-Sun Wong, Jun Yu

{"title":"A blood-based biomarker panel for non-invasive diagnosis of metabolic dysfunction-associated steatohepatitis","authors":"Xiang Zhang, Ming-Hua Zheng, Dehua Liu, Yufeng Lin, Sherlot Juan Song, Eagle Siu-Hong Chu, Dabin Liu, Seema Singh, Michael Berman, Harry Cheuk-Hay Lau, Hongyan Gou, Grace Lai-Hung Wong, Ni Zhang, Hai-Yang Yuan, Rohit Loomba, Vincent Wai-Sun Wong, Jun Yu","doi":"10.1016/j.cmet.2024.10.008","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.10.008","url":null,"abstract":"The current diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) and its severe form, metabolic dysfunction-associated steatohepatitis (MASH), is suboptimal. Here, we recruited 700 individuals, including 184 from Hong Kong as a discovery cohort and 516 from San Diego, Wenzhou, and Hong Kong as three validation cohorts. A panel of 3 parameters (C-X-C motif chemokine ligand 10 [CXCL10], cytokeratin 18 fragments M30 [CK-18], and adjusted body mass index [BMI]) was formulated (termed N3-MASH), which discriminated patients with MASLD from healthy controls with an area under the receiver operating characteristic (AUROC) of 0.954. Among patients with MASLD, N3-MASH could identify patients with MASH with an AUROC of 0.823, achieving 90.0% specificity, 62.9% sensitivity, and 88.6% positive predictive value. The diagnostic performance of N3-MASH was confirmed in three validation cohorts with AUROC of 0.802, 0.805, and 0.823, respectively. Additionally, N3-MASH identifies patients with MASH improvement with an AUROC of 0.857. In summary, we developed a robust blood-based panel for the non-invasive diagnosis of MASH, which might help clinicians reduce unnecessary liver biopsies.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"27 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hyperglycemia-triggered lipid peroxidation destabilizes STAT4 and impairs anti-viral Th1 responses in type 2 diabetes 高血糖引发的脂质过氧化会破坏 STAT4 的稳定性并损害 2 型糖尿病患者的 Th1 抗病毒反应

IF 29 1区生物学

Cell metabolism Pub Date : 2024-11-01 DOI: 10.1016/j.cmet.2024.10.004

Victor Gray, Weixin Chen, Rachael Julia Yuenyinn Tan, Jia Ming Nickolas Teo, Zhihao Huang, Carol Ho-Yi Fong, Tommy Wing Hang Law, Zi-Wei Ye, Shuofeng Yuan, Xiucong Bao, Ivan Fan-Ngai Hung, Kathryn Choon-Beng Tan, Chi-Ho Lee, Guang Sheng Ling

{"title":"Hyperglycemia-triggered lipid peroxidation destabilizes STAT4 and impairs anti-viral Th1 responses in type 2 diabetes","authors":"Victor Gray, Weixin Chen, Rachael Julia Yuenyinn Tan, Jia Ming Nickolas Teo, Zhihao Huang, Carol Ho-Yi Fong, Tommy Wing Hang Law, Zi-Wei Ye, Shuofeng Yuan, Xiucong Bao, Ivan Fan-Ngai Hung, Kathryn Choon-Beng Tan, Chi-Ho Lee, Guang Sheng Ling","doi":"10.1016/j.cmet.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.10.004","url":null,"abstract":"Patients with type 2 diabetes (T2D) are more susceptible to severe respiratory viral infections, but the underlying mechanisms remain elusive. Here, we show that patients with T2D and coronavirus disease 2019 (COVID-19) infections, and influenza-infected T2D mice, exhibit defective T helper 1 (Th1) responses, which are an essential component of anti-viral immunity. This defect stems from intrinsic metabolic perturbations in CD4+ T cells driven by hyperglycemia. Mechanistically, hyperglycemia triggers mitochondrial dysfunction and excessive fatty acid synthesis, leading to elevated oxidative stress and aberrant lipid accumulation within CD4+ T cells. These abnormalities promote lipid peroxidation (LPO), which drives carbonylation of signal transducer and activator of transcription 4 (STAT4), a crucial Th1-lineage-determining factor. Carbonylated STAT4 undergoes rapid degradation, causing reduced T-bet induction and diminished Th1 differentiation. LPO scavenger ameliorates Th1 defects in patients with T2D who have poor glycemic control and restores viral control in T2D mice. Thus, this hyperglycemia-LPO-STAT4 axis underpins reduced Th1 activity in T2D hosts, with important implications for managing T2D-related viral complications.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"192 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plasma protein-based organ-specific aging and mortality models unveil diseases as accelerated aging of organismal systems 基于血浆蛋白的器官特异性衰老和死亡模型揭示了疾病是机体系统加速衰老的表现

IF 29 1区生物学

Cell metabolism Pub Date : 2024-11-01 DOI: 10.1016/j.cmet.2024.10.005

Ludger J.E. Goeminne, Anastasiya Vladimirova, Alec Eames, Alexander Tyshkovskiy, M. Austin Argentieri, Kejun Ying, Mahdi Moqri, Vadim N. Gladyshev

{"title":"Plasma protein-based organ-specific aging and mortality models unveil diseases as accelerated aging of organismal systems","authors":"Ludger J.E. Goeminne, Anastasiya Vladimirova, Alec Eames, Alexander Tyshkovskiy, M. Austin Argentieri, Kejun Ying, Mahdi Moqri, Vadim N. Gladyshev","doi":"10.1016/j.cmet.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.10.005","url":null,"abstract":"Aging is a complex process manifesting at molecular, cellular, organ, and organismal levels. It leads to functional decline, disease, and ultimately death, but the relationship between these fundamental biomedical features remains elusive. By applying elastic net regularization to plasma proteome data of over 50,000 human subjects in the UK Biobank and other cohorts, we report interpretable organ-specific and conventional aging models trained on chronological age, mortality, and longitudinal proteome data. These models predict organ/system-specific disease and indicate that men age faster than women in most organs. Accelerated organ aging leads to diseases in these organs, and specific diets, lifestyles, professions, and medications influence organ aging rates. We then identify proteins driving these associations with organ-specific aging. Our analyses reveal that age-related chronic diseases epitomize accelerated organ- and system-specific aging, modifiable through environmental factors, advocating for both universal whole-organism and personalized organ/system-specific anti-aging interventions.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"126 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anti-seizure effects of norepinephrine-induced free fatty acid release 去甲肾上腺素诱导游离脂肪酸释放的抗癫痫作用

IF 29 1区生物学

Cell metabolism Pub Date : 2024-10-31 DOI: 10.1016/j.cmet.2024.10.011

Baoman Li, Qian Sun, Fengfei Ding, Qiwu Xu, Ning Kang, Yang Xue, Antonio Ladron-de-Guevara, Hajime Hirase, Pia Weikop, Sheng Gong, Smith Nathan, Maiken Nedergaard

引用次数: 0

Bempedoic acid suppresses diet-induced hepatic steatosis independently of ATP-citrate lyase 双鱼藤酸抑制饮食诱导的肝脂肪变性，与 ATP 柠檬酸裂解酶无关

IF 29 1区生物学

Cell metabolism Pub Date : 2024-10-28 DOI: 10.1016/j.cmet.2024.10.014

Joyce Y. Liu, Ramya S. Kuna, Laura V. Pinheiro, Phuong T.T. Nguyen, Jaclyn E. Welles, Jack M. Drummond, Nivitha Murali, Prateek Sharma, Julianna G. Supplee, Mia Shiue, Steven Zhao, Aimee T. Farria, Avi Kumar, Mauren L. Ruchhoeft, Christina Demetriadou, Daniel S. Kantner, Adam Chatoff, Emily Megill, Paul M. Titchenell, Nathaniel W. Snyder, Kathryn E. Wellen

{"title":"Bempedoic acid suppresses diet-induced hepatic steatosis independently of ATP-citrate lyase","authors":"Joyce Y. Liu, Ramya S. Kuna, Laura V. Pinheiro, Phuong T.T. Nguyen, Jaclyn E. Welles, Jack M. Drummond, Nivitha Murali, Prateek Sharma, Julianna G. Supplee, Mia Shiue, Steven Zhao, Aimee T. Farria, Avi Kumar, Mauren L. Ruchhoeft, Christina Demetriadou, Daniel S. Kantner, Adam Chatoff, Emily Megill, Paul M. Titchenell, Nathaniel W. Snyder, Kathryn E. Wellen","doi":"10.1016/j.cmet.2024.10.014","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.10.014","url":null,"abstract":"ATP citrate lyase (ACLY) synthesizes acetyl-CoA for de novo lipogenesis (DNL), which is elevated in metabolic dysfunction-associated steatotic liver disease. Hepatic ACLY is inhibited by the LDL-cholesterol-lowering drug bempedoic acid (BPA), which also improves steatosis in mice. While BPA potently suppresses hepatic DNL and increases fat catabolism, it is unclear if ACLY is its primary molecular target in reducing liver triglyceride. We show that on a Western diet, loss of hepatic ACLY alone or together with the acetyl-CoA synthetase ACSS2 unexpectedly exacerbates steatosis, linked to reduced PPARα target gene expression and fatty acid oxidation. Importantly, BPA treatment ameliorates Western diet-mediated triacylglyceride accumulation in both WT and liver ACLY knockout mice, indicating that its primary effects on hepatic steatosis are ACLY independent. Together, these data indicate that hepatic ACLY plays an unexpected role in restraining diet-dependent lipid accumulation and that BPA exerts substantial effects on hepatic lipid metabolism independently of ACLY.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"15 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A hierarchical hepatic de novo lipogenesis substrate supply network utilizing pyruvate, acetate, and ketones 利用丙酮酸、乙酸和酮的分层肝脏新生脂肪生成底物供应网络

IF 29 1区生物学

Cell metabolism Pub Date : 2024-10-28 DOI: 10.1016/j.cmet.2024.10.013

Adam J. Rauckhorst, Ryan D. Sheldon, Daniel J. Pape, Adnan Ahmed, Kelly C. Falls-Hubert, Ronald A. Merrill, Reid F. Brown, Kshitij Deshmukh, Thomas A. Vallim, Stanislaw Deja, Shawn C. Burgess, Eric B. Taylor

{"title":"A hierarchical hepatic de novo lipogenesis substrate supply network utilizing pyruvate, acetate, and ketones","authors":"Adam J. Rauckhorst, Ryan D. Sheldon, Daniel J. Pape, Adnan Ahmed, Kelly C. Falls-Hubert, Ronald A. Merrill, Reid F. Brown, Kshitij Deshmukh, Thomas A. Vallim, Stanislaw Deja, Shawn C. Burgess, Eric B. Taylor","doi":"10.1016/j.cmet.2024.10.013","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.10.013","url":null,"abstract":"Hepatic de novo lipogenesis (DNL) is a fundamental physiologic process that is often pathogenically elevated in metabolic disease. Treatment is limited by incomplete understanding of the metabolic pathways supplying cytosolic acetyl-CoA, the obligate precursor to DNL, including their interactions and proportional contributions. Here, we combined extensive 13C tracing with liver-specific knockout of key mitochondrial and cytosolic proteins mediating cytosolic acetyl-CoA production. We show that the mitochondrial pyruvate carrier (MPC) and ATP-citrate lyase (ACLY) gate the major hepatic lipogenic acetyl-CoA production pathway, operating in parallel with acetyl-CoA synthetase 2 (ACSS2). Given persistent DNL after mitochondrial citrate carrier (CiC) and ACSS2 double knockout, we tested the contribution of exogenous and leucine-derived acetoacetate to acetoacetyl-CoA synthetase (AACS)-dependent DNL. CiC knockout increased acetoacetate-supplied hepatic acetyl-CoA production and DNL, indicating that ketones function as mitochondrial-citrate reciprocal DNL precursors. By delineating a mitochondrial-cytosolic DNL substrate supply network, these findings may inform strategies to therapeutically modulate DNL.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"4 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hexokinase 2 senses fructose in tumor-associated macrophages to promote colorectal cancer growth 己糖激酶 2 能感知肿瘤相关巨噬细胞中的果糖，从而促进结直肠癌的生长

IF 29 1区生物学

Cell metabolism Pub Date : 2024-10-28 DOI: 10.1016/j.cmet.2024.10.002

Huiwen Yan, Zhi Wang, Da Teng, Xiaodong Chen, Zijing Zhu, Huan Chen, Wen Wang, Ziyuan Wei, Zhenzhen Wu, Qian Chai, Fei Zhang, Youwang Wang, Kaile Shu, Shaotang Li, Guizhi Shi, Mingzhao Zhu, Hai-long Piao, Xian Shen, Pengcheng Bu

{"title":"Hexokinase 2 senses fructose in tumor-associated macrophages to promote colorectal cancer growth","authors":"Huiwen Yan, Zhi Wang, Da Teng, Xiaodong Chen, Zijing Zhu, Huan Chen, Wen Wang, Ziyuan Wei, Zhenzhen Wu, Qian Chai, Fei Zhang, Youwang Wang, Kaile Shu, Shaotang Li, Guizhi Shi, Mingzhao Zhu, Hai-long Piao, Xian Shen, Pengcheng Bu","doi":"10.1016/j.cmet.2024.10.002","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.10.002","url":null,"abstract":"Fructose is associated with colorectal cancer tumorigenesis and metastasis through ketohexokinase-mediated metabolism in the colorectal epithelium, yet its role in the tumor immune microenvironment remains largely unknown. Here, we show that a modest amount of fructose, without affecting obesity and associated complications, promotes colorectal cancer tumorigenesis and growth by suppressing the polarization of M1-like macrophages. Fructose inhibits M1-like macrophage polarization independently of fructose-mediated metabolism. Instead, it serves as a signal molecule to promote the interaction between hexokinase 2 and inositol 1,4,5-trisphophate receptor type 3, the predominant Ca2+ channel on the endoplasmic reticulum. The interaction reduces Ca2+ levels in cytosol and mitochondria, thereby suppressing the activation of mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 1 (STAT1) as well as NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. Consequently, this impedes M1-like macrophage polarization. Our study highlights the critical role of fructose as a signaling molecule that impairs the polarization of M1-like macrophages for tumor growth.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"61 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0