Cell metabolism最新文献_第10页

A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1 5:2间歇性禁食疗法可通过肝脏PPARα和PCK1改善NASH和纤维化，并减弱HCC的发展

IF 29 1区生物学

Cell metabolism Pub Date : 2024-05-07 DOI: 10.1016/j.cmet.2024.04.015

Suchira Gallage, Adnan Ali, Jose Efren Barragan Avila, Nogayhan Seymen, Pierluigi Ramadori, Vera Joerke, Laimdota Zizmare, David Aicher, Indresh K. Gopalsamy, Winnie Fong, Jan Kosla, Enrico Focaccia, Xin Li, Suhail Yousuf, Tjeerd Sijmonsma, Mohammad Rahbari, Katharina S. Kommoss, Adrian Billeter, Sandra Prokosch, Ulrike Rothermel, Mathias Heikenwalder

{"title":"A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1","authors":"Suchira Gallage, Adnan Ali, Jose Efren Barragan Avila, Nogayhan Seymen, Pierluigi Ramadori, Vera Joerke, Laimdota Zizmare, David Aicher, Indresh K. Gopalsamy, Winnie Fong, Jan Kosla, Enrico Focaccia, Xin Li, Suhail Yousuf, Tjeerd Sijmonsma, Mohammad Rahbari, Katharina S. Kommoss, Adrian Billeter, Sandra Prokosch, Ulrike Rothermel, Mathias Heikenwalder","doi":"10.1016/j.cmet.2024.04.015","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.04.015","url":null,"abstract":"The role and molecular mechanisms of intermittent fasting (IF) in non-alcoholic steatohepatitis (NASH) and its transition to hepatocellular carcinoma (HCC) are unknown. Here, we identified that an IF 5:2 regimen prevents NASH development as well as ameliorates established NASH and fibrosis without affecting total calorie intake. Furthermore, the IF 5:2 regimen blunted NASH-HCC transition when applied therapeutically. The timing, length, and number of fasting cycles as well as the type of NASH diet were critical parameters determining the benefits of fasting. Combined proteome, transcriptome, and metabolome analyses identified that peroxisome-proliferator-activated receptor alpha (PPARα) and glucocorticoid-signaling-induced PCK1 act co-operatively as hepatic executors of the fasting response. In line with this, PPARα targets and PCK1 were reduced in human NASH. Notably, only fasting initiated during the active phase of mice robustly induced glucocorticoid signaling and free-fatty-acid-induced PPARα signaling. However, hepatocyte-specific glucocorticoid receptor deletion only partially abrogated the hepatic fasting response. In contrast, the combined knockdown of Ppara and Pck1 in vivo abolished the beneficial outcomes of fasting against inflammation and fibrosis. Moreover, overexpression of Pck1 alone or together with Ppara in vivo lowered hepatic triglycerides and steatosis. Our data support the notion that the IF 5:2 regimen is a promising intervention against NASH and subsequent liver cancer.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":null,"pages":null},"PeriodicalIF":29.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846114","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

Branching out beyond canonical brown adipocyte function 超越典型棕色脂肪细胞功能的分支

IF 29 1区生物学

Cell metabolism Pub Date : 2024-05-07 DOI: 10.1016/j.cmet.2024.04.011

Helaina Von Bank, Judith Simcox

引用次数: 0

Dysregulated BH4 metabolism facilitates immunosuppression in pancreatic cancer BH4 代谢失调有助于胰腺癌的免疫抑制

IF 29 1区生物学

Cell metabolism Pub Date : 2024-05-07 DOI: 10.1016/j.cmet.2024.04.009

Shane J.F. Cronin

引用次数: 0

Understanding osteokine biology 了解骨生成素生物学

IF 29 1区生物学

Cell metabolism Pub Date : 2024-05-07 DOI: 10.1016/j.cmet.2024.04.008

Mone Zaidi, Samir Zaidi, Tony Yuen

引用次数: 0

Hepatic selective insulin resistance at the intersection of insulin signaling and metabolic dysfunction-associated steatotic liver disease 肝脏选择性胰岛素抵抗是胰岛素信号传导与代谢功能障碍相关脂肪性肝病的交叉点

IF 29 1区生物学

Cell metabolism Pub Date : 2024-05-07 DOI: 10.1016/j.cmet.2024.04.006

Tao Bo, Ling Gao, Zhenyu Yao, Shanshan Shao, Xuemin Wang, Christopher G. Proud, Jiajun Zhao

引用次数: 0

Diabetic retinopathy is a ceramidopathy reversible by anti-ceramide immunotherapy 糖尿病视网膜病变是一种可通过抗神经酰胺免疫疗法逆转的神经酰胺病变

IF 29 1区生物学

Cell metabolism Pub Date : 2024-05-07 DOI: 10.1016/j.cmet.2024.04.013

Tim F. Dorweiler, Arjun Singh, Aditya Ganju, Todd A. Lydic, Louis C. Glazer, Richard N. Kolesnick, Julia V. Busik

{"title":"Diabetic retinopathy is a ceramidopathy reversible by anti-ceramide immunotherapy","authors":"Tim F. Dorweiler, Arjun Singh, Aditya Ganju, Todd A. Lydic, Louis C. Glazer, Richard N. Kolesnick, Julia V. Busik","doi":"10.1016/j.cmet.2024.04.013","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.04.013","url":null,"abstract":"Diabetic retinopathy is a microvascular disease that causes blindness. Using acid sphingomyelinase knockout mice, we reported that ceramide generation is critical for diabetic retinopathy development. Here, in patients with proliferative diabetic retinopathy, we identify vitreous ceramide imbalance with pathologic long-chain C16-ceramides increasing and protective very long-chain C26-ceramides decreasing. C16-ceramides generate pro-inflammatory/pro-apoptotic ceramide-rich platforms on endothelial surfaces. To geo-localize ceramide-rich platforms, we invented a three-dimensional confocal assay and showed that retinopathy-producing cytokines TNFα and IL-1β induce ceramide-rich platform formation on retinal endothelial cells within seconds, with volumes increasing 2-logs, yielding apoptotic death. Anti-ceramide antibodies abolish these events. Furthermore, intravitreal and systemic anti-ceramide antibodies protect from diabetic retinopathy in standardized rodent ischemia reperfusion and streptozotocin models. These data support (1) retinal endothelial ceramide as a diabetic retinopathy treatment target, (2) early-stage therapy of non-proliferative diabetic retinopathy to prevent progression, and (3) systemic diabetic retinopathy treatment; and they characterize diabetic retinopathy as a “ceramidopathy” reversible by anti-ceramide immunotherapy.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":null,"pages":null},"PeriodicalIF":29.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846143","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

Gut microbial alterations in arginine metabolism determine bone mechanical adaptation 精氨酸代谢中的肠道微生物变化决定骨机械适应性

IF 29 1区生物学

Cell metabolism Pub Date : 2024-05-07 DOI: 10.1016/j.cmet.2024.04.004

Dan Wang, Jing Cai, Qilin Pei, Zedong Yan, Feng Zhu, Zhe Zhao, Ruobing Liu, Xiangyang Guo, Tao Sun, Juan Liu, Yulan Tian, Hongbo Liu, Xi Shao, Jinghui Huang, Xiaoxia Hao, Qi Chang, Zhuojing Luo, Da Jing

{"title":"Gut microbial alterations in arginine metabolism determine bone mechanical adaptation","authors":"Dan Wang, Jing Cai, Qilin Pei, Zedong Yan, Feng Zhu, Zhe Zhao, Ruobing Liu, Xiangyang Guo, Tao Sun, Juan Liu, Yulan Tian, Hongbo Liu, Xi Shao, Jinghui Huang, Xiaoxia Hao, Qi Chang, Zhuojing Luo, Da Jing","doi":"10.1016/j.cmet.2024.04.004","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.04.004","url":null,"abstract":"Although mechanical loading is essential for maintaining bone health and combating osteoporosis, its practical application is limited to a large extent by the high variability in bone mechanoresponsiveness. Here, we found that gut microbial depletion promoted a significant reduction in skeletal adaptation to mechanical loading. Among experimental mice, we observed differences between those with high and low responses to exercise with respect to the gut microbial composition, in which the differential abundance of Lachnospiraceae contributed to the differences in bone mechanoresponsiveness. Microbial production of L-citrulline and its conversion into L-arginine were identified as key regulators of bone mechanoadaptation, and administration of these metabolites enhanced bone mechanoresponsiveness in normal, aged, and ovariectomized mice. Mechanistically, L-arginine-mediated enhancement of bone mechanoadaptation was primarily attributable to the activation of a nitric-oxide-calcium positive feedback loop in osteocytes. This study identifies a promising anti-osteoporotic strategy for maximizing mechanical loading-induced skeletal benefits via the microbiota-metabolite axis.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":null,"pages":null},"PeriodicalIF":29.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846206","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

Targeting metabolic circuitry to supercharge CD8+ T cell antitumor responses 以代谢回路为目标，增强 CD8+ T 细胞的抗肿瘤反应

IF 29 1区生物学

Cell metabolism Pub Date : 2024-05-07 DOI: 10.1016/j.cmet.2024.04.007

Qiang Cai, Yihao Tian, Quazi T.H. Shubhra

引用次数: 0

Obesity disrupts the pituitary-hepatic UPR communication leading to NAFLD progression 肥胖会破坏垂体-肝脏 UPR 通信，导致非酒精性脂肪肝恶化

IF 29 1区生物学

Cell metabolism Pub Date : 2024-05-07 DOI: 10.1016/j.cmet.2024.04.014

Qingwen Qian, Mark Li, Zeyuan Zhang, Shannon W. Davis, Kamal Rahmouni, Andrew W. Norris, Huojun Cao, Wen-Xing Ding, Gökhan S. Hotamisligil, Ling Yang

{"title":"Obesity disrupts the pituitary-hepatic UPR communication leading to NAFLD progression","authors":"Qingwen Qian, Mark Li, Zeyuan Zhang, Shannon W. Davis, Kamal Rahmouni, Andrew W. Norris, Huojun Cao, Wen-Xing Ding, Gökhan S. Hotamisligil, Ling Yang","doi":"10.1016/j.cmet.2024.04.014","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.04.014","url":null,"abstract":"Obesity alters levels of pituitary hormones that govern hepatic immune-metabolic homeostasis, dysregulation of which leads to nonalcoholic fatty liver disease (NAFLD). However, the impact of obesity on intra-pituitary homeostasis is largely unknown. Here, we uncovered a blunted unfolded protein response (UPR) but elevated inflammatory signatures in pituitary glands of obese mice and humans. Furthermore, we found that obesity inflames the pituitary gland, leading to impaired pituitary inositol-requiring enzyme 1α (IRE1α)-X-box-binding protein 1 (XBP1) UPR branch, which is essential for protecting against pituitary endocrine defects and NAFLD progression. Intriguingly, pituitary IRE1-deletion resulted in hypothyroidism and suppressed the thyroid hormone receptor B (THRB)-mediated activation of Xbp1 in the liver. Conversely, activation of the hepatic THRB-XBP1 axis improved NAFLD in mice with pituitary UPR defect. Our study provides the first evidence and mechanism of obesity-induced intra-pituitary cellular defects and the pathophysiological role of pituitary-liver UPR communication in NAFLD progression.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":null,"pages":null},"PeriodicalIF":29.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846203","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 novel protein CYTB-187AA encoded by the mitochondrial gene CYTB modulates mammalian early development 线粒体基因 CYTB 编码的新型蛋白质 CYTB-187AA 调节哺乳动物的早期发育

IF 29 1区生物学

Cell metabolism Pub Date : 2024-05-03 DOI: 10.1016/j.cmet.2024.04.012

Zhijuan Hu, Liang Yang, Maolei Zhang, Haite Tang, Yile Huang, Yujie Su, Yingzhe Ding, Chong Li, Mengfei Wang, Yunhao Zhou, Qing Zhang, Liman Guo, Yue Wu, Qianqian Wang, Ning Liu, Haoran Kang, Yi Wu, Deyang Yao, Yukun Li, Zifeng Ruan, Xingguo Liu

{"title":"A novel protein CYTB-187AA encoded by the mitochondrial gene CYTB modulates mammalian early development","authors":"Zhijuan Hu, Liang Yang, Maolei Zhang, Haite Tang, Yile Huang, Yujie Su, Yingzhe Ding, Chong Li, Mengfei Wang, Yunhao Zhou, Qing Zhang, Liman Guo, Yue Wu, Qianqian Wang, Ning Liu, Haoran Kang, Yi Wu, Deyang Yao, Yukun Li, Zifeng Ruan, Xingguo Liu","doi":"10.1016/j.cmet.2024.04.012","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.04.012","url":null,"abstract":"The mitochondrial genome transcribes 13 mRNAs coding for well-known proteins essential for oxidative phosphorylation. We demonstrate here that cytochrome b (CYTB), the only mitochondrial-DNA-encoded transcript among complex III, also encodes an unrecognized 187-amino-acid-long protein, CYTB-187AA, using the standard genetic code of cytosolic ribosomes rather than the mitochondrial genetic code. After validating the existence of this mtDNA-encoded protein arising from cytosolic translation (mPACT) using mass spectrometry and antibodies, we show that CYTB-187AA is mainly localized in the mitochondrial matrix and promotes the pluripotent state in primed-to-naive transition by interacting with solute carrier family 25 member 3 (SLC25A3) to modulate ATP production. We further generated a transgenic knockin mouse model of CYTB-187AA silencing and found that reduction of CYTB-187AA impairs females’ fertility by decreasing the number of ovarian follicles. For the first time, we uncovered the novel mPACT pattern of a mitochondrial mRNA and demonstrated the physiological function of this 14th protein encoded by mtDNA.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":null,"pages":null},"PeriodicalIF":29.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821239","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