Cell metabolism最新文献_第6页

The PNPLA3 I148M variant increases ketogenesis and decreases hepatic de novo lipogenesis and mitochondrial function in humans. PNPLA3 I148M变体增加了人类的酮体生成，降低了肝脏的新生脂肪生成和线粒体功能。

Cell metabolism Pub Date : 2023-11-07 Epub Date: 2023-10-30 DOI: 10.1016/j.cmet.2023.10.008

Panu K Luukkonen, Kimmo Porthan, Noora Ahlholm, Fredrik Rosqvist, Sylvie Dufour, Xian-Man Zhang, Tiina E Lehtimäki, Wenla Seppänen, Marju Orho-Melander, Leanne Hodson, Kitt Falk Petersen, Gerald I Shulman, Hannele Yki-Järvinen

{"title":"The PNPLA3 I148M variant increases ketogenesis and decreases hepatic de novo lipogenesis and mitochondrial function in humans.","authors":"Panu K Luukkonen, Kimmo Porthan, Noora Ahlholm, Fredrik Rosqvist, Sylvie Dufour, Xian-Man Zhang, Tiina E Lehtimäki, Wenla Seppänen, Marju Orho-Melander, Leanne Hodson, Kitt Falk Petersen, Gerald I Shulman, Hannele Yki-Järvinen","doi":"10.1016/j.cmet.2023.10.008","DOIUrl":"10.1016/j.cmet.2023.10.008","url":null,"abstract":"The PNPLA3 I148M variant is the major genetic risk factor for all stages of fatty liver disease, but the underlying pathophysiology remains unclear. We studied the effect of this variant on hepatic metabolism in homozygous carriers and non-carriers under multiple physiological conditions with state-of-the-art stable isotope techniques. After an overnight fast, carriers had higher plasma β-hydroxybutyrate concentrations and lower hepatic de novo lipogenesis (DNL) compared to non-carriers. After a mixed meal, fatty acids were channeled toward ketogenesis in carriers, which was associated with an increase in hepatic mitochondrial redox state. During a ketogenic diet, carriers manifested increased rates of intrahepatic lipolysis, increased plasma β-hydroxybutyrate concentrations, and decreased rates of hepatic mitochondrial citrate synthase flux. These studies demonstrate that homozygous PNPLA3 I148M carriers have hepatic mitochondrial dysfunction leading to reduced DNL and channeling of carbons to ketogenesis. These findings have implications for understanding why the PNPLA3 variant predisposes to progressive liver disease.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"1887-1896.e5"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71430185","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

The bidirectional immune crosstalk in metabolic dysfunction-associated steatotic liver disease. 代谢功能障碍相关脂肪变性肝病的双向免疫串扰。

Cell metabolism Pub Date : 2023-11-07 DOI: 10.1016/j.cmet.2023.10.009

Keisuke Sawada, Hak Chung, Samir Softic, Maria E Moreno-Fernandez, Senad Divanovic

引用次数: 0

Bone marrow immune cells stop weight regain. 骨髓免疫细胞阻止体重恢复。

Cell metabolism Pub Date : 2023-11-07 DOI: 10.1016/j.cmet.2023.10.004

Jing Yan, Cheng Hu

引用次数: 1

CD36 maintains lipid homeostasis via selective uptake of monounsaturated fatty acids during matrix detachment and tumor progression. CD36在基质分离和肿瘤进展过程中通过选择性摄取单不饱和脂肪酸来维持脂质稳态。

Cell metabolism Pub Date : 2023-11-07 Epub Date: 2023-10-17 DOI: 10.1016/j.cmet.2023.09.012

Alexander R Terry, Veronique Nogueira, Hyunsoo Rho, Gopalakrishnan Ramakrishnan, Jing Li, Soeun Kang, Koralege C Pathmasiri, Sameer Ahmed Bhat, Liping Jiang, Shafi Kuchay, Stephanie M Cologna, Nissim Hay

{"title":"CD36 maintains lipid homeostasis via selective uptake of monounsaturated fatty acids during matrix detachment and tumor progression.","authors":"Alexander R Terry, Veronique Nogueira, Hyunsoo Rho, Gopalakrishnan Ramakrishnan, Jing Li, Soeun Kang, Koralege C Pathmasiri, Sameer Ahmed Bhat, Liping Jiang, Shafi Kuchay, Stephanie M Cologna, Nissim Hay","doi":"10.1016/j.cmet.2023.09.012","DOIUrl":"10.1016/j.cmet.2023.09.012","url":null,"abstract":"A high-fat diet (HFD) promotes metastasis through increased uptake of saturated fatty acids (SFAs). The fatty acid transporter CD36 has been implicated in this process, but a detailed understanding of CD36 function is lacking. During matrix detachment, endoplasmic reticulum (ER) stress reduces SCD1 protein, resulting in increased lipid saturation. Subsequently, CD36 is induced in a p38- and AMPK-dependent manner to promote preferential uptake of monounsaturated fatty acids (MUFAs), thereby maintaining a balance between SFAs and MUFAs. In attached cells, CD36 palmitoylation is required for MUFA uptake and protection from palmitate-induced lipotoxicity. In breast cancer mouse models, CD36-deficiency induced ER stress while diminishing the pro-metastatic effect of HFD, and only a palmitoylation-proficient CD36 rescued this effect. Finally, AMPK-deficient tumors have reduced CD36 expression and are metastatically impaired, but ectopic CD36 expression restores their metastatic potential. Our results suggest that, rather than facilitating HFD-driven tumorigenesis, CD36 plays a supportive role by preventing SFA-induced lipotoxicity.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"2060-2076.e9"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686263","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

High dietary fructose promotes hepatocellular carcinoma progression by enhancing O-GlcNAcylation via microbiota-derived acetate. 高膳食果糖通过微生物群衍生的乙酸盐增强O-GlcNAcylation，从而促进肝细胞癌的进展。

Cell metabolism Pub Date : 2023-11-07 Epub Date: 2023-10-04 DOI: 10.1016/j.cmet.2023.09.009

Peng Zhou, Wen-Yi Chang, De-Ao Gong, Jie Xia, Wei Chen, Lu-Yi Huang, Rui Liu, Yi Liu, Chang Chen, Kai Wang, Ni Tang, Ai-Long Huang

{"title":"High dietary fructose promotes hepatocellular carcinoma progression by enhancing O-GlcNAcylation via microbiota-derived acetate.","authors":"Peng Zhou, Wen-Yi Chang, De-Ao Gong, Jie Xia, Wei Chen, Lu-Yi Huang, Rui Liu, Yi Liu, Chang Chen, Kai Wang, Ni Tang, Ai-Long Huang","doi":"10.1016/j.cmet.2023.09.009","DOIUrl":"10.1016/j.cmet.2023.09.009","url":null,"abstract":"Emerging studies have addressed the tumor-promoting role of fructose in different cancers. The effects and pathological mechanisms of high dietary fructose on hepatocellular carcinoma (HCC) remain unclear. Here, we examined the effects of fructose supplementation on HCC progression in wild-type C57BL/6 mice using a spontaneous and chemically induced HCC mouse model. We show that elevated uridine diphospho-N-acetylglucosamine (UDP-GlcNAc) and O-GlcNAcylation levels induced by high dietary fructose contribute to HCC progression. Non-targeted metabolomics and stable isotope tracing revealed that under fructose treatment, microbiota-derived acetate upregulates glutamine and UDP-GlcNAc levels and enhances protein O-GlcNAcylation in HCC. Global profiling of O-GlcNAcylation revealed that hyper-O-GlcNAcylation of eukaryotic elongation factor 1A1 promotes cell proliferation and tumor growth. Targeting glutamate-ammonia ligase or O-linked N-acetylglucosamine transferase (OGT) remarkably impeded HCC progression in mice with high fructose intake. We propose that high dietary fructose promotes HCC progression through microbial acetate-induced hyper-O-GlcNAcylation.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"1961-1975.e6"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41168727","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: 1

Regenerating the heart by metabolically reprogramming the cardiomyocyte epigenome. 通过对心肌细胞表观基因组进行代谢重新编程来再生心脏。

Cell metabolism Pub Date : 2023-11-07 DOI: 10.1016/j.cmet.2023.10.007

Xiaoqiang Tang

引用次数: 0

Comprehensive quantification of metabolic flux during acute cold stress in mice. 小鼠急性冷应激期间代谢通量的综合量化。

Cell metabolism Pub Date : 2023-11-07 Epub Date: 2023-10-05 DOI: 10.1016/j.cmet.2023.09.002

Marc R Bornstein, Michael D Neinast, Xianfeng Zeng, Qingwei Chu, Jessie Axsom, Chelsea Thorsheim, Kristina Li, Megan C Blair, Joshua D Rabinowitz, Zoltan Arany

{"title":"Comprehensive quantification of metabolic flux during acute cold stress in mice.","authors":"Marc R Bornstein, Michael D Neinast, Xianfeng Zeng, Qingwei Chu, Jessie Axsom, Chelsea Thorsheim, Kristina Li, Megan C Blair, Joshua D Rabinowitz, Zoltan Arany","doi":"10.1016/j.cmet.2023.09.002","DOIUrl":"10.1016/j.cmet.2023.09.002","url":null,"abstract":"Cold-induced thermogenesis (CIT) is widely studied as a potential avenue to treat obesity, but a thorough understanding of the metabolic changes driving CIT is lacking. Here, we present a comprehensive and quantitative analysis of the metabolic response to acute cold exposure, leveraging metabolomic profiling and minimally perturbative isotope tracing studies in unanesthetized mice. During cold exposure, brown adipose tissue (BAT) primarily fueled the tricarboxylic acid (TCA) cycle with fat in fasted mice and glucose in fed mice, underscoring BAT's metabolic flexibility. BAT minimally used branched-chain amino acids or ketones, which were instead avidly consumed by muscle during cold exposure. Surprisingly, isotopic labeling analyses revealed that BAT uses glucose largely for TCA anaplerosis via pyruvate carboxylation. Finally, we find that cold-induced hepatic gluconeogenesis is critical for CIT during fasting, demonstrating a key functional role for glucose metabolism. Together, these findings provide a detailed map of the metabolic rewiring driving acute CIT.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"2077-2092.e6"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10840821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41168571","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

Metabolic support by macrophages sustains colonic epithelial homeostasis. 巨噬细胞的代谢支持维持结肠上皮稳态。

Cell metabolism Pub Date : 2023-11-07 Epub Date: 2023-10-06 DOI: 10.1016/j.cmet.2023.09.010

Stephanie Deborah Fritsch, Nyamdelger Sukhbaatar, Karine Gonzales, Alishan Sahu, Loan Tran, Andrea Vogel, Mario Mazic, Jayne Louise Wilson, Stephan Forisch, Hannah Mayr, Raimund Oberle, Jakob Weiszmann, Martin Brenner, Roeland Vanhoutte, Melanie Hofmann, Sini Pirnes-Karhu, Christoph Magnes, Torben Kühnast, Wolfram Weckwerth, Christoph Bock, Kristaps Klavins, Markus Hengstschläger, Christine Moissl-Eichinger, Gernot Schabbauer, Gerda Egger, Eija Pirinen, Steven H L Verhelst, Thomas Weichhart

{"title":"Metabolic support by macrophages sustains colonic epithelial homeostasis.","authors":"Stephanie Deborah Fritsch, Nyamdelger Sukhbaatar, Karine Gonzales, Alishan Sahu, Loan Tran, Andrea Vogel, Mario Mazic, Jayne Louise Wilson, Stephan Forisch, Hannah Mayr, Raimund Oberle, Jakob Weiszmann, Martin Brenner, Roeland Vanhoutte, Melanie Hofmann, Sini Pirnes-Karhu, Christoph Magnes, Torben Kühnast, Wolfram Weckwerth, Christoph Bock, Kristaps Klavins, Markus Hengstschläger, Christine Moissl-Eichinger, Gernot Schabbauer, Gerda Egger, Eija Pirinen, Steven H L Verhelst, Thomas Weichhart","doi":"10.1016/j.cmet.2023.09.010","DOIUrl":"10.1016/j.cmet.2023.09.010","url":null,"abstract":"The intestinal epithelium has a high turnover rate and constantly renews itself through proliferation of intestinal crypt cells, which depends on insufficiently characterized signals from the microenvironment. Here, we showed that colonic macrophages were located directly adjacent to epithelial crypt cells in mice, where they metabolically supported epithelial cell proliferation in an mTORC1-dependent manner. Specifically, deletion of tuberous sclerosis complex 2 (Tsc2) in macrophages activated mTORC1 signaling that protected against colitis-induced intestinal damage and induced the synthesis of the polyamines spermidine and spermine. Epithelial cells ingested these polyamines and rewired their cellular metabolism to optimize proliferation and defense. Notably, spermine directly stimulated proliferation of colon epithelial cells and colon organoids. Genetic interference with polyamine production in macrophages altered global polyamine levels in the colon and modified epithelial cell proliferation. Our results suggest that macrophages act as \"commensals\" that provide metabolic support to promote efficient self-renewal of the colon epithelium.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"1931-1943.e8"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41165102","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: 2

Skeletal muscle-derived extracellular vesicles transport glycolytic enzymes to mediate muscle-to-bone crosstalk. 骨骼肌衍生的细胞外小泡运输糖酵解酶以介导肌骨串扰。

Cell metabolism Pub Date : 2023-11-07 DOI: 10.1016/j.cmet.2023.10.013

Shixing Ma, Xiaotao Xing, Haisen Huang, Xin Gao, Xun Xu, Jian Yang, Chengcheng Liao, Xuanhao Zhang, Jinglun Liu, Weidong Tian, Li Liao

{"title":"Skeletal muscle-derived extracellular vesicles transport glycolytic enzymes to mediate muscle-to-bone crosstalk.","authors":"Shixing Ma, Xiaotao Xing, Haisen Huang, Xin Gao, Xun Xu, Jian Yang, Chengcheng Liao, Xuanhao Zhang, Jinglun Liu, Weidong Tian, Li Liao","doi":"10.1016/j.cmet.2023.10.013","DOIUrl":"10.1016/j.cmet.2023.10.013","url":null,"abstract":"Identification of cues originating from skeletal muscle that govern bone formation is essential for understanding the crosstalk between muscle and bone and for developing therapies for degenerative bone diseases. Here, we identified that skeletal muscle secreted multiple extracellular vesicles (Mu-EVs). These Mu-EVs traveled through the bloodstream to reach bone, where they were phagocytized by bone marrow mesenchymal stem/stromal cells (BMSCs). Mu-EVs promoted osteogenic differentiation of BMSCs and protected against disuse osteoporosis in mice. The quantity and bioactivity of Mu-EVs were tightly correlated with the function of skeletal muscle. Proteomic analysis revealed numerous proteins in Mu-EVs, some potentially regulating bone metabolism, especially glycolysis. Subsequent investigations indicated that Mu-EVs promoted the glycolysis of BMSCs by delivering lactate dehydrogenase A into these cells. In summary, these findings reveal that Mu-EVs play a vital role in BMSC metabolism regulation and bone formation stimulation, offering a promising approach for treating disuse osteoporosis.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":"35 11","pages":"2028-2043.e7"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71523775","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

Colonic macrophages eat and feed. 结肠巨噬细胞进食和进食。

Cell metabolism Pub Date : 2023-11-07 DOI: 10.1016/j.cmet.2023.10.006

Jan Van den Bossche

引用次数: 0