Cell metabolism最新文献_第6页

m6A mRNA methylation in brown fat regulates systemic insulin sensitivity via an inter-organ prostaglandin signaling axis independent of UCP1 棕色脂肪中的 m6A mRNA 甲基化通过独立于 UCP1 的器官间前列腺素信号轴调节全身胰岛素敏感性

IF 29 1区生物学

Cell metabolism Pub Date : 2024-09-09 DOI: 10.1016/j.cmet.2024.08.006

Ling Xiao, Dario F. De Jesus, Cheng-Wei Ju, Jiang Bo Wei, Jiang Hu, Ava DiStefano-Forti, Tadataka Tsuji, Cheryl Cero, Ville Männistö, Suvi M. Manninen, Siying Wei, Oluwaseun Ijaduola, Matthias Blüher, Aaron M. Cypess, Jussi Pihlajamäki, Yu-Hua Tseng, Chuan He, Rohit N. Kulkarni

{"title":"m6A mRNA methylation in brown fat regulates systemic insulin sensitivity via an inter-organ prostaglandin signaling axis independent of UCP1","authors":"Ling Xiao, Dario F. De Jesus, Cheng-Wei Ju, Jiang Bo Wei, Jiang Hu, Ava DiStefano-Forti, Tadataka Tsuji, Cheryl Cero, Ville Männistö, Suvi M. Manninen, Siying Wei, Oluwaseun Ijaduola, Matthias Blüher, Aaron M. Cypess, Jussi Pihlajamäki, Yu-Hua Tseng, Chuan He, Rohit N. Kulkarni","doi":"10.1016/j.cmet.2024.08.006","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.08.006","url":null,"abstract":"Brown adipose tissue (BAT) regulates systemic metabolism by releasing signaling lipids. N6-methyladenosine (m6A) is the most prevalent and abundant post-transcriptional mRNA modification and has been reported to regulate BAT adipogenesis and energy expenditure. Here, we demonstrate that the absence of m6A methyltransferase-like 14 (METTL14) modifies the BAT secretome to improve systemic insulin sensitivity independent of UCP1. Using lipidomics, we identify prostaglandin E2 (PGE2) and prostaglandin F2a (PGF2a) as BAT-secreted insulin sensitizers. PGE2 and PGF2a inversely correlate with insulin sensitivity in humans and protect mice from high-fat-diet-induced insulin resistance by suppressing specific AKT phosphatases. Mechanistically, METTL14-mediated m6A promotes the decay of PTGES2 and CBR1, the genes encoding PGE2 and PGF2a biosynthesis enzymes, in brown adipocytes via YTHDF2/3. Consistently, BAT-specific knockdown of Ptges2 or Cbr1 reverses the insulin-sensitizing effects in M14KO mice. Overall, these findings reveal a novel biological mechanism through which m6A-dependent regulation of the BAT secretome regulates systemic insulin sensitivity.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"17 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158712","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

SGLT2 inhibitor promotes ketogenesis to improve MASH by suppressing CD8+ T cell activation SGLT2 抑制剂通过抑制 CD8+ T 细胞活化促进酮体生成以改善 MASH

IF 29 1区生物学

Cell metabolism Pub Date : 2024-09-06 DOI: 10.1016/j.cmet.2024.08.005

Wenhui Liu, Danming You, Jiayang Lin, Huren Zou, Lei Zhang, Shenjian Luo, Youwen Yuan, Zhiyi Wang, Jingwen Qi, Weiwei Wang, Xueru Ye, Xiaoyu Yang, Yajuan Deng, Fei Teng, Xiaojun Zheng, Yuhao Lin, Zhiwei Huang, Yan Huang, Zhi Yang, Xuan Zhou, Huijie Zhang

{"title":"SGLT2 inhibitor promotes ketogenesis to improve MASH by suppressing CD8+ T cell activation","authors":"Wenhui Liu, Danming You, Jiayang Lin, Huren Zou, Lei Zhang, Shenjian Luo, Youwen Yuan, Zhiyi Wang, Jingwen Qi, Weiwei Wang, Xueru Ye, Xiaoyu Yang, Yajuan Deng, Fei Teng, Xiaojun Zheng, Yuhao Lin, Zhiwei Huang, Yan Huang, Zhi Yang, Xuan Zhou, Huijie Zhang","doi":"10.1016/j.cmet.2024.08.005","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.08.005","url":null,"abstract":"During the progression of metabolic dysfunction-associated steatohepatitis (MASH), the accumulation of auto-aggressive CD8+ T cells significantly contributes to liver injury and inflammation. Empagliflozin (EMPA), a highly selective inhibitor of sodium-glucose co-transporter 2 (SGLT2), exhibits potential therapeutic benefits for liver steatosis; however, the underlying mechanism remains incompletely elucidated. Here, we found that EMPA significantly reduced the hepatic accumulation of auto-aggressive CD8+ T cells and lowered granzyme B levels in mice with MASH. Mechanistically, EMPA increased β-hydroxybutyric acid by promoting the ketogenesis of CD8+ T cells via elevating 3-hydroxybutyrate dehydrogenase 1 (Bdh1) expression. The β-hydroxybutyric acid subsequently inhibited interferon regulatory factor 4 (Irf4), which is crucial for CD8+ T cell activation. Furthermore, the ablation of Bdh1 in T cells aggravated the manifestation of MASH and hindered the therapeutic efficacy of EMPA. Moreover, a case-control study also showed that SGLT2 inhibitor treatment repressed CD8+ T cell infiltration and improved liver injury in patients with MASH. In summary, our study indicates that SGLT2 inhibitors can target CD8+ T cells and may be an effective strategy for treating MASH.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"7 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142862","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

Bacteroides acidifaciens: Linking dietary fiber to liver health 酸性乳杆菌：膳食纤维与肝脏健康的联系

IF 29 1区生物学

Cell metabolism Pub Date : 2024-09-03 DOI: 10.1016/j.cmet.2024.08.002

Viacheslav A. Petrov, Cédric C. Laczny, Paul Wilmes

引用次数: 0

The crosstalk between metabolism and translation 新陈代谢与翻译之间的相互影响

IF 29 1区生物学

Cell metabolism Pub Date : 2024-09-03 DOI: 10.1016/j.cmet.2024.07.022

Stefano Biffo, Davide Ruggero, Massimo Mattia Santoro

引用次数: 0

Multi-organ transcriptome atlas of a mouse model of relative energy deficiency in sport 运动中能量相对缺乏小鼠模型的多器官转录组图谱

IF 29 1区生物学

Cell metabolism Pub Date : 2024-09-03 DOI: 10.1016/j.cmet.2024.08.001

Laura van Rosmalen, Jiaoyue Zhu, Geraldine Maier, Erica G. Gacasan, Terry Lin, Elena Zhemchuzhnikova, Vince Rothenberg, Swithin Razu, Shaunak Deota, Ramesh K. Ramasamy, Robert L. Sah, Andrew D. McCulloch, Roelof A. Hut, Satchidananda Panda

{"title":"Multi-organ transcriptome atlas of a mouse model of relative energy deficiency in sport","authors":"Laura van Rosmalen, Jiaoyue Zhu, Geraldine Maier, Erica G. Gacasan, Terry Lin, Elena Zhemchuzhnikova, Vince Rothenberg, Swithin Razu, Shaunak Deota, Ramesh K. Ramasamy, Robert L. Sah, Andrew D. McCulloch, Roelof A. Hut, Satchidananda Panda","doi":"10.1016/j.cmet.2024.08.001","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.08.001","url":null,"abstract":"Insufficient energy intake to meet energy expenditure demands of physical activity can result in systemic neuroendocrine and metabolic abnormalities in activity-dependent anorexia and relative energy deficiency in sport (REDs). REDs affects >40% of athletes, yet the lack of underlying molecular changes has been a hurdle to have a better understanding of REDs and its treatment. To assess the molecular changes in response to energy deficiency, we implemented the “exercise-for-food” paradigm, in which food reward size is determined by wheel-running activity. By using this paradigm, we replicated several aspects of REDs in female and male mice with high physical activity and gradually reduced food intake, which results in weight loss, compromised bone health, organ-specific mass changes, and altered rest-activity patterns. By integrating transcriptomics of 19 different organs, we provide a comprehensive dataset that will guide future understanding of REDs and may provide important implications for metabolic health and (athletic) performance.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"8 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123927","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

Defying “IL-11ness” by inhibiting inflammation: Strategy for health and longevity 通过抑制炎症对抗 "IL-11"：健康与长寿战略

IF 29 1区生物学

Cell metabolism Pub Date : 2024-09-03 DOI: 10.1016/j.cmet.2024.08.003

Hee-Hoon Kim, Vishwa Deep Dixit

引用次数: 0

Gene-metabolite linkage marks stored red blood cell quality 基因-代谢物联系标志着储存的红细胞质量

IF 29 1区生物学

Cell metabolism Pub Date : 2024-09-03 DOI: 10.1016/j.cmet.2024.08.004

Changhan Chen, Wuping Liu, Yang Xia

引用次数: 0

Glucagon promotes increased hepatic mitochondrial oxidation and pyruvate carboxylase flux in humans with fatty liver disease 胰高血糖素促进脂肪肝患者肝线粒体氧化和丙酮酸羧化酶通量的增加

IF 29 1区生物学

Cell metabolism Pub Date : 2024-08-27 DOI: 10.1016/j.cmet.2024.07.023

Kitt Falk Petersen, Sylvie Dufour, Wajahat Z. Mehal, Gerald I. Shulman

{"title":"Glucagon promotes increased hepatic mitochondrial oxidation and pyruvate carboxylase flux in humans with fatty liver disease","authors":"Kitt Falk Petersen, Sylvie Dufour, Wajahat Z. Mehal, Gerald I. Shulman","doi":"10.1016/j.cmet.2024.07.023","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.07.023","url":null,"abstract":"We assessed in vivo rates of hepatic mitochondrial oxidation, gluconeogenesis, and β-hydroxybutyrate (β-OHB) turnover by positional isotopomer NMR tracer analysis (PINTA) in individuals with metabolic-dysfunction-associated steatotic liver (MASL) (fatty liver) and MASL disease (MASLD) (steatohepatitis) compared with BMI-matched control participants with no hepatic steatosis. Hepatic fat content was quantified by localized 1H magnetic resonance spectroscopy (MRS). We found that in vivo rates of hepatic mitochondrial oxidation were unaltered in the MASL and MASLD groups compared with the control group. A physiological increase in plasma glucagon concentrations increased in vivo rates of hepatic mitochondrial oxidation by 50%–75% in individuals with and without MASL and increased rates of glucose production by ∼50% in the MASL group, which could be attributed in part to an ∼30% increase in rates of mitochondrial pyruvate carboxylase flux. These results demonstrate that (1) rates of hepatic mitochondrial oxidation are not substantially altered in individuals with MASL and MASLD and (2) glucagon increases rates of hepatic mitochondrial oxidation.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"16 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142084969","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 nutrigeroscience approach: Dietary macronutrients and cellular senescence 营养学方法：膳食宏量营养素与细胞衰老

IF 29 1区生物学

Cell metabolism Pub Date : 2024-08-22 DOI: 10.1016/j.cmet.2024.07.025

Mariah F. Calubag, Paul D. Robbins, Dudley W. Lamming

引用次数: 0

Mitochondrial membrane lipids in the regulation of bioenergetic flux 线粒体膜脂在生物能通量调节中的作用

IF 29 1区生物学

Cell metabolism Pub Date : 2024-08-22 DOI: 10.1016/j.cmet.2024.07.024

Stephen Thomas Decker, Katsuhiko Funai

引用次数: 0