Cell metabolism最新文献_第4页

Supercharging cancer-fighting T cells with lithium carbonate. 用碳酸锂为抗癌 T 细胞充电。

Cell metabolism Pub Date : 2024-03-05 DOI: 10.1016/j.cmet.2024.02.006

Yue Xu, Kaili Ma, Lianjun Zhang, Guideng Li

引用次数: 0

UCP1 and CKB are parallel players in BAT. UCP1 和 CKB 是 BAT 的并行参与者。

Cell metabolism Pub Date : 2024-03-05 DOI: 10.1016/j.cmet.2024.01.016

Meng Dong, Ziyu Cheng, Wanzhu Jin

引用次数: 0

Parallel control of cold-triggered adipocyte thermogenesis by UCP1 and CKB. UCP1 和 CKB 并行控制冷触发的脂肪细胞产热。

Cell metabolism Pub Date : 2024-03-05 Epub Date: 2024-01-24 DOI: 10.1016/j.cmet.2024.01.001

Janane F Rahbani, Jakub Bunk, Damien Lagarde, Bozena Samborska, Anna Roesler, Haopeng Xiao, Abhirup Shaw, Zafir Kaiser, Jessica L Braun, Mia S Geromella, Val A Fajardo, Robert A Koza, Lawrence Kazak

{"title":"Parallel control of cold-triggered adipocyte thermogenesis by UCP1 and CKB.","authors":"Janane F Rahbani, Jakub Bunk, Damien Lagarde, Bozena Samborska, Anna Roesler, Haopeng Xiao, Abhirup Shaw, Zafir Kaiser, Jessica L Braun, Mia S Geromella, Val A Fajardo, Robert A Koza, Lawrence Kazak","doi":"10.1016/j.cmet.2024.01.001","DOIUrl":"10.1016/j.cmet.2024.01.001","url":null,"abstract":"That uncoupling protein 1 (UCP1) is the sole mediator of adipocyte thermogenesis is a conventional viewpoint that has primarily been inferred from the attenuation of the thermogenic output of mice genetically lacking Ucp1 from birth (germline Ucp1-/-). However, germline Ucp1-/- mice harbor secondary changes within brown adipose tissue. To mitigate these potentially confounding ancillary changes, we constructed mice with inducible adipocyte-selective Ucp1 disruption. We find that, although germline Ucp1-/- mice succumb to cold-induced hypothermia with complete penetrance, most mice with the inducible deletion of Ucp1 maintain homeothermy in the cold. However, inducible adipocyte-selective co-deletion of Ucp1 and creatine kinase b (Ckb, an effector of UCP1-independent thermogenesis) exacerbates cold intolerance. Following UCP1 deletion or UCP1/CKB co-deletion from mature adipocytes, moderate cold exposure triggers the regeneration of mature brown adipocytes that coordinately restore UCP1 and CKB expression. Our findings suggest that thermogenic adipocytes utilize non-paralogous protein redundancy-through UCP1 and CKB-to promote cold-induced energy dissipation.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"526-540.e7"},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139565319","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

Lysine acetyltransferase 6A maintains CD4⁺ T cell response via epigenetic reprogramming of glucose metabolism in autoimmunity. 赖氨酸乙酰转移酶 6A 通过对自身免疫中的葡萄糖代谢进行表观遗传学重编程来维持 CD4+ T 细胞反应。

Cell metabolism Pub Date : 2024-03-05 Epub Date: 2024-01-17 DOI: 10.1016/j.cmet.2023.12.016

Jia-Yao Fu, Shi-Jia Huang, Bao-Li Wang, Jun-Hao Yin, Chang-Yu Chen, Jia-Bao Xu, Yan-Lin Chen, Shuo Xu, Ting Dong, Hao-Nan Zhou, Xin-Yi Ma, Yi-Ping Pu, Hui Li, Xiu-Juan Yang, Li-Song Xie, Zhi-Jun Wang, Qi Luo, Yan-Xiong Shao, Lei Ye, Zi-Rui Zong, Xin-Di Wei, Wan-Wen Xiao, Shu-Tong Niu, Yi-Ming Liu, He-Ping Xu, Chuang-Qi Yu, Sheng-Zhong Duan, Ling-Yan Zheng

{"title":"Lysine acetyltransferase 6A maintains CD4+ T cell response via epigenetic reprogramming of glucose metabolism in autoimmunity.","authors":"Jia-Yao Fu, Shi-Jia Huang, Bao-Li Wang, Jun-Hao Yin, Chang-Yu Chen, Jia-Bao Xu, Yan-Lin Chen, Shuo Xu, Ting Dong, Hao-Nan Zhou, Xin-Yi Ma, Yi-Ping Pu, Hui Li, Xiu-Juan Yang, Li-Song Xie, Zhi-Jun Wang, Qi Luo, Yan-Xiong Shao, Lei Ye, Zi-Rui Zong, Xin-Di Wei, Wan-Wen Xiao, Shu-Tong Niu, Yi-Ming Liu, He-Ping Xu, Chuang-Qi Yu, Sheng-Zhong Duan, Ling-Yan Zheng","doi":"10.1016/j.cmet.2023.12.016","DOIUrl":"10.1016/j.cmet.2023.12.016","url":null,"abstract":"Augmented CD4+ T cell response in autoimmunity is characterized by extensive metabolic reprogramming. However, the epigenetic molecule that drives the metabolic adaptation of CD4+ T cells remains largely unknown. Here, we show that lysine acetyltransferase 6A (KAT6A), an epigenetic modulator that is clinically associated with autoimmunity, orchestrates the metabolic reprogramming of glucose in CD4+ T cells. KAT6A is required for the proliferation and differentiation of proinflammatory CD4+ T cell subsets in vitro, and mice with KAT6A-deficient CD4+ T cells are less susceptible to experimental autoimmune encephalomyelitis and colitis. Mechanistically, KAT6A orchestrates the abundance of histone acetylation at the chromatin where several glycolytic genes are located, thus affecting glucose metabolic reprogramming and subsequent CD4+ T cell responses. Treatment with KAT6A small-molecule inhibitors in mouse models shows high therapeutic value for targeting KAT6A in autoimmunity. Our study provides novel insights into the epigenetic programming of immunometabolism and suggests potential therapeutic targets for patients with autoimmunity.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"557-574.e10"},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139492936","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

DGAT2 inhibition blocks SREBP-1 cleavage and improves hepatic steatosis by increasing phosphatidylethanolamine in the ER. 抑制 DGAT2 可阻止 SREBP-1 的裂解，并通过增加 ER 中的磷脂酰乙醇胺来改善肝脏脂肪变性。

Cell metabolism Pub Date : 2024-03-05 Epub Date: 2024-02-09 DOI: 10.1016/j.cmet.2024.01.011

Shunxing Rong, Mingfeng Xia, Goncalo Vale, Simeng Wang, Chai-Wan Kim, Shili Li, Jeffrey G McDonald, Arun Radhakrishnan, Jay D Horton

{"title":"DGAT2 inhibition blocks SREBP-1 cleavage and improves hepatic steatosis by increasing phosphatidylethanolamine in the ER.","authors":"Shunxing Rong, Mingfeng Xia, Goncalo Vale, Simeng Wang, Chai-Wan Kim, Shili Li, Jeffrey G McDonald, Arun Radhakrishnan, Jay D Horton","doi":"10.1016/j.cmet.2024.01.011","DOIUrl":"10.1016/j.cmet.2024.01.011","url":null,"abstract":"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. ER enrichment with PE blocked SREBP-1 cleavage independent of Insigs, which are ER proteins that normally retain SREBPs in the ER. Thus, inhibition of DGAT2 shunted diacylglycerol into phospholipid synthesis, increasing the PE content of the ER, resulting in reduced SREBP-1 cleavage and less hepatic steatosis. This study reveals a new mechanism that regulates SREBP-1 activation and lipogenesis that is independent of sterols and SREBP-2 in liver.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"617-629.e7"},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10939742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716696","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

Carnosine facilitates lysosomal release of inhibitors of T cell surveillance. 肉碱能促进溶酶体释放 T 细胞监视抑制剂。

Cell metabolism Pub Date : 2024-03-05 DOI: 10.1016/j.cmet.2024.02.003

Pawel Swietach, Marja Jäättelä, Shari Pillon-Thomas, Ebbe Boedtkjer

引用次数: 0

Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus. 猕猴下丘脑对肥胖和糖尿病的特定区域转录组反应

Cell metabolism Pub Date : 2024-02-06 DOI: 10.1016/j.cmet.2024.01.003

Ying Lei, Xian Liang, Yunong Sun, Ting Yao, Hongyu Gong, Zhenhua Chen, Yuanqing Gao, Hui Wang, Ru Wang, Yunqi Huang, Tao Yang, Miao Yu, Longqi Liu, Chun-Xia Yi, Qing-Feng Wu, Xingxing Kong, Xun Xu, Shiping Liu, Zhi Zhang, Tiemin Liu

{"title":"Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus.","authors":"Ying Lei, Xian Liang, Yunong Sun, Ting Yao, Hongyu Gong, Zhenhua Chen, Yuanqing Gao, Hui Wang, Ru Wang, Yunqi Huang, Tao Yang, Miao Yu, Longqi Liu, Chun-Xia Yi, Qing-Feng Wu, Xingxing Kong, Xun Xu, Shiping Liu, Zhi Zhang, Tiemin Liu","doi":"10.1016/j.cmet.2024.01.003","DOIUrl":"10.1016/j.cmet.2024.01.003","url":null,"abstract":"The hypothalamus plays a crucial role in the progression of obesity and diabetes; however, its structural complexity and cellular heterogeneity impede targeted treatments. Here, we profiled the single-cell and spatial transcriptome of the hypothalamus in obese and sporadic type 2 diabetic macaques, revealing primate-specific distributions of clusters and genes as well as spatial region, cell-type-, and gene-feature-specific changes. The infundibular (INF) and paraventricular nuclei (PVN) are most susceptible to metabolic disruption, with the PVN being more sensitive to diabetes. In the INF, obesity results in reduced synaptic plasticity and energy sensing capability, whereas diabetes involves molecular reprogramming associated with impaired tanycytic barriers, activated microglia, and neuronal inflammatory response. In the PVN, cellular metabolism and neural activity are suppressed in diabetic macaques. Spatial transcriptomic data reveal microglia's preference for the parenchyma over the third ventricle in diabetes. Our findings provide a comprehensive view of molecular changes associated with obesity and diabetes.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":"36 2","pages":"438-453.e6"},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704217","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

Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating. 肠道和大脑分别强化脂肪和糖分的回路，共同促进了暴饮暴食。

Cell metabolism Pub Date : 2024-02-06 Epub Date: 2024-01-18 DOI: 10.1016/j.cmet.2023.12.014

Molly McDougle, Alan de Araujo, Arashdeep Singh, Mingxin Yang, Isadora Braga, Vincent Paille, Rebeca Mendez-Hernandez, Macarena Vergara, Lauren N Woodie, Abhishek Gour, Abhisheak Sharma, Nikhil Urs, Brandon Warren, Guillaume de Lartigue

{"title":"Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating.","authors":"Molly McDougle, Alan de Araujo, Arashdeep Singh, Mingxin Yang, Isadora Braga, Vincent Paille, Rebeca Mendez-Hernandez, Macarena Vergara, Lauren N Woodie, Abhishek Gour, Abhisheak Sharma, Nikhil Urs, Brandon Warren, Guillaume de Lartigue","doi":"10.1016/j.cmet.2023.12.014","DOIUrl":"10.1016/j.cmet.2023.12.014","url":null,"abstract":"Food is a powerful natural reinforcer that guides feeding decisions. The vagus nerve conveys internal sensory information from the gut to the brain about nutritional value; however, the cellular and molecular basis of macronutrient-specific reward circuits is poorly understood. Here, we monitor in vivo calcium dynamics to provide direct evidence of independent vagal sensing pathways for the detection of dietary fats and sugars. Using activity-dependent genetic capture of vagal neurons activated in response to gut infusions of nutrients, we demonstrate the existence of separate gut-brain circuits for fat and sugar sensing that are necessary and sufficient for nutrient-specific reinforcement. Even when controlling for calories, combined activation of fat and sugar circuits increases nigrostriatal dopamine release and overeating compared with fat or sugar alone. This work provides new insights into the complex sensory circuitry that mediates motivated behavior and suggests that a subconscious internal drive to consume obesogenic diets (e.g., those high in both fat and sugar) may impede conscious dieting efforts.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"393-407.e7"},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139502624","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

Ketone flux through BDH1 supports metabolic remodeling of skeletal and cardiac muscles in response to intermittent time-restricted feeding. 通过 BDH1 的酮通量支持骨骼肌和心肌对间歇性限时进食的代谢重塑。

Cell metabolism Pub Date : 2024-02-06 DOI: 10.1016/j.cmet.2024.01.007

Ashley S Williams, Scott B Crown, Scott P Lyons, Timothy R Koves, Rebecca J Wilson, Jordan M Johnson, Dorothy H Slentz, Daniel P Kelly, Paul A Grimsrud, Guo-Fang Zhang, Deborah M Muoio

{"title":"Ketone flux through BDH1 supports metabolic remodeling of skeletal and cardiac muscles in response to intermittent time-restricted feeding.","authors":"Ashley S Williams, Scott B Crown, Scott P Lyons, Timothy R Koves, Rebecca J Wilson, Jordan M Johnson, Dorothy H Slentz, Daniel P Kelly, Paul A Grimsrud, Guo-Fang Zhang, Deborah M Muoio","doi":"10.1016/j.cmet.2024.01.007","DOIUrl":"10.1016/j.cmet.2024.01.007","url":null,"abstract":"Time-restricted feeding (TRF) has gained attention as a dietary regimen that promotes metabolic health. This study questioned if the health benefits of an intermittent TRF (iTRF) schedule require ketone flux specifically in skeletal and cardiac muscles. Notably, we found that the ketolytic enzyme beta-hydroxybutyrate dehydrogenase 1 (BDH1) is uniquely enriched in isolated mitochondria derived from heart and red/oxidative skeletal muscles, which also have high capacity for fatty acid oxidation (FAO). Using mice with BDH1 deficiency in striated muscles, we discover that this enzyme optimizes FAO efficiency and exercise tolerance during acute fasting. Additionally, iTRF leads to robust molecular remodeling of muscle tissues, and muscle BDH1 flux does indeed play an essential role in conferring the full adaptive benefits of this regimen, including increased lean mass, mitochondrial hormesis, and metabolic rerouting of pyruvate. In sum, ketone flux enhances mitochondrial bioenergetics and supports iTRF-induced remodeling of skeletal muscle and heart.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":"36 2","pages":"422-437.e8"},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704216","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

Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism. 线粒体脂肪酸合成是哺乳动物氧化代谢的一个新兴中心调节因子。

Cell metabolism Pub Date : 2024-01-02 Epub Date: 2023-12-20 DOI: 10.1016/j.cmet.2023.11.017

Riley J Wedan, Jacob Z Longenecker, Sara M Nowinski

引用次数: 0