Jing Zhang, Yu Wang, Meiyang Fan, Yanglong Guan, Wentao Zhang, Fumeng Huang, Zhengqiang Zhang, Xiaomeng Li, Bingyu Yuan, Wenbin Liu, Manman Geng, Xiaowei Li, Jing Xu, Congshan Jiang, Wenjuan Zhao, Feng Ye, Wenhua Zhu, Liesu Meng, Shemin Lu, Rikard Holmdahl
Impaired self-renewal of Kupffer cells (KCs) leads to inflammation in metabolic dysfunction-associated steatohepatitis (MASH). Here, we identify neutrophil cytosolic factor 1 (NCF1) as a critical regulator of iron homeostasis in KCs. NCF1 is upregulated in liver macrophages and dendritic cells in humans with metabolic dysfunction-associated steatotic liver disease and in MASH mice. Macrophage NCF1, but not dendritic cell NCF1, triggers KC iron overload, ferroptosis, and monocyte-derived macrophage infiltration, thus aggravating MASH progression...
June 4, 2024: Cell Metabolism
Paul Horn, Frank Tacke
Chronic liver diseases, primarily metabolic dysfunction-associated steatotic liver disease (MASLD), harmful use of alcohol, or viral hepatitis, may result in liver fibrosis, cirrhosis, and cancer. Hepatic fibrogenesis is a complex process with interactions between different resident and non-resident heterogeneous liver cell populations, ultimately leading to deposition of extracellular matrix and organ failure. Shifts in cell phenotypes and functions involve pronounced transcriptional and protein synthesis changes that require metabolic adaptations in cellular substrate metabolism, including glucose and lipid metabolism, resembling changes associated with the Warburg effect in cancer cells...
May 27, 2024: Cell Metabolism
Elaine Zaunseder, Ulrike Mütze, Jürgen G Okun, Georg F Hoffmann, Stefan Kölker, Vincent Heuveline, Ines Thiele
Comprehensive whole-body models (WBMs) accounting for organ-specific dynamics have been developed to simulate adult metabolism, but such models do not exist for infants. Here, we present a resource of 360 organ-resolved, sex-specific models of newborn and infant metabolism (infant-WBMs) spanning the first 180 days of life. These infant-WBMs were parameterized to represent the distinct metabolic characteristics of newborns and infants, including nutrition, energy requirements, and thermoregulation. We demonstrate that the predicted infant growth was consistent with the recommendation by the World Health Organization...
May 25, 2024: Cell Metabolism
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
No abstract text is available yet for this article.
May 17, 2024: Cell Metabolism
Fei Peng, Jinxin Lu, Keyu Su, Xinyu Liu, Huandong Luo, Bin He, Cenxin Wang, Xiaoyu Zhang, Fan An, Dekang Lv, Yuanyuan Luo, Qitong Su, Tonghui Jiang, Ziqian Deng, Bin He, Lingzhi Xu, Tao Guo, Jin Xiang, Chundong Gu, Ling Wang, Guowang Xu, Ying Xu, Mindian Li, Keith W Kelley, Bai Cui, Quentin Liu
Circadian disruption predicts poor cancer prognosis, yet how circadian disruption is sensed in sleep-deficiency (SD)-enhanced tumorigenesis remains obscure. Here, we show fatty acid oxidation (FAO) as a circadian sensor relaying from clock disruption to oncogenic metabolic signal in SD-enhanced lung tumorigenesis. Both unbiased transcriptomic and metabolomic analyses reveal that FAO senses SD-induced circadian disruption, as illustrated by continuously increased palmitoyl-coenzyme A (PA-CoA) catalyzed by long-chain fatty acyl-CoA synthetase 1 (ACSL1)...
May 14, 2024: Cell Metabolism
Radiana Ferrero, Pernille Yde Rainer, Marie Rumpler, Julie Russeil, Magda Zachara, Joern Pezoldt, Guido van Mierlo, Vincent Gardeux, Wouter Saelens, Daniel Alpern, Lucie Favre, Nathalie Vionnet, Styliani Mantziari, Tobias Zingg, Nelly Pitteloud, Michel Suter, Maurice Matter, Kai-Uwe Schlaudraff, Carles Canto, Bart Deplancke
Adipose tissue plasticity is orchestrated by molecularly and functionally diverse cells within the stromal vascular fraction (SVF). Although several mouse and human adipose SVF cellular subpopulations have by now been identified, we still lack an understanding of the cellular and functional variability of adipose stem and progenitor cell (ASPC) populations across human fat depots. To address this, we performed single-cell and bulk RNA sequencing (RNA-seq) analyses of >30 SVF/Lin- samples across four human adipose depots, revealing two ubiquitous human ASPC (hASPC) subpopulations with distinct proliferative and adipogenic properties but also depot- and BMI-dependent proportions...
May 8, 2024: Cell Metabolism
Qingwen Qian, Mark Li, Zeyuan Zhang, Shannon W Davis, Kamal Rahmouni, Andrew W Norris, Huojun Cao, Wen-Xing Ding, Gökhan S Hotamisligil, Ling Yang
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...
May 3, 2024: Cell Metabolism
Tim F Dorweiler, Arjun Singh, Aditya Ganju, Todd A Lydic, Louis C Glazer, Richard N Kolesnick, Julia V Busik
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...
May 3, 2024: Cell Metabolism
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
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...
May 2, 2024: Cell Metabolism
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, Florian Mueller, Jenny Hetzer, Danijela Heide, Benjamin Schinkel, Tim Machauer, Bernd Pichler, Nisar P Malek, Thomas Longerich, Susanne Roth, Adam J Rose, Johannes Schwenck, Christoph Trautwein, Mohammad M Karimi, Mathias Heikenwalder
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...
May 2, 2024: Cell Metabolism
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, Hao Wang, Feixiang Bao, Guopan Liu, Junwei Wang, Yaofeng Wang, Wuming Wang, Gang Lu, Dajiang Qin, Duanqing Pei, Wai-Yee Chan, Xingguo Liu
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...
April 29, 2024: Cell Metabolism
Monica A Tincopa, Quentin M Anstee, Rohit Loomba
No abstract text is available yet for this article.
April 25, 2024: Cell Metabolism
Nesrine S Rachedi, Ying Tang, Yi-Yin Tai, Jingsi Zhao, Caroline Chauvet, Julien Grynblat, Kouamé Kan Firmin Akoumia, Leonard Estephan, Stéphanie Torrino, Chaima Sbai, Amel Ait-Mouffok, Joseph D Latoche, Yassmin Al Aaraj, Frederic Brau, Sophie Abélanet, Stephan Clavel, Yingze Zhang, Christelle Guillermier, Naveen V G Kumar, Sina Tavakoli, Olaf Mercier, Michael G Risbano, Zhong-Ke Yao, Guangli Yang, Ouathek Ouerfelli, Jason S Lewis, David Montani, Marc Humbert, Matthew L Steinhauser, Carolyn J Anderson, William M Oldham, Frédéric Perros, Thomas Bertero, Stephen Y Chan
Perivascular collagen deposition by activated fibroblasts promotes vascular stiffening and drives cardiovascular diseases such as pulmonary hypertension (PH). Whether and how vascular fibroblasts rewire their metabolism to sustain collagen biosynthesis remains unknown. Here, we found that inflammation, hypoxia, and mechanical stress converge on activating the transcriptional coactivators YAP and TAZ (WWTR1) in pulmonary arterial adventitial fibroblasts (PAAFs). Consequently, YAP and TAZ drive glutamine and serine catabolism to sustain proline and glycine anabolism and promote collagen biosynthesis...
April 24, 2024: Cell Metabolism
Erik A Richter, David E James, John P Kirwan, Juleen R Zierath
No abstract text is available yet for this article.
April 16, 2024: Cell Metabolism
Yajuan Li, Daniel Munoz-Mayorga, Yuhang Nie, Ningxin Kang, Yuren Tao, Jessica Lagerwall, Carla Pernaci, Genevieve Curtin, Nicole G Coufal, Jerome Mertens, Lingyan Shi, Xu Chen
The accumulation of lipid droplets (LDs) in aging and Alzheimer's disease brains is considered a pathological phenomenon with unresolved cellular and molecular mechanisms. Utilizing stimulated Raman scattering (SRS) microscopy, we observed significant in situ LD accumulation in microglia of tauopathy mouse brains. SRS imaging, combined with deuterium oxide (D2 O) labeling, revealed heightened lipogenesis and impaired lipid turnover within LDs in tauopathy fly brains and human neurons derived from induced pluripotent stem cells (iPSCs)...
April 16, 2024: Cell Metabolism
Ji Liu, Xiaowei He, Shuang Deng, Sihan Zhao, Shaoping Zhang, Ziming Chen, Chunling Xue, Lingxing Zeng, Hongzhe Zhao, Yifan Zhou, Ruihong Bai, Zilan Xu, Shaoqiu Liu, Quanbo Zhou, Mei Li, Jialiang Zhang, Xudong Huang, Rufu Chen, Liqin Wang, Dongxin Lin, Jian Zheng
The relevance of biopterin metabolism in resistance to immune checkpoint blockade (ICB) therapy remains unknown. We demonstrate that the deficiency of quinoid dihydropteridine reductase (QDPR), a critical enzyme regulating biopterin metabolism, causes metabolite dihydrobiopterin (BH2) accumulation and decreases the ratio of tetrahydrobiopterin (BH4) to BH2 in pancreatic ductal adenocarcinomas (PDACs). The reduced BH4/BH2 ratio leads to an increase in reactive oxygen species (ROS) generation and a decrease in the distribution of H3K27me3 at CXCL1 promoter...
April 15, 2024: Cell Metabolism
Zhen Lu, Noreen McBrearty, Jinyun Chen, Vivek S Tomar, Hongru Zhang, Gianluca De Rosa, Aiwen Tan, Aalim M Weljie, Daniel P Beiting, Zhen Miao, Subin S George, Allison Berger, Gurpanna Saggu, J Alan Diehl, Constantinos Koumenis, Serge Y Fuchs
No abstract text is available yet for this article.
April 10, 2024: Cell Metabolism
Wanyu Tao, Zhengqing Yu, Jing-Dong J Han
Cellular senescence underlies many aging-related pathologies, but its heterogeneity poses challenges for studying and targeting senescent cells. We present here a machine learning program senescent cell identification (SenCID), which accurately identifies senescent cells in both bulk and single-cell transcriptome. Trained on 602 samples from 52 senescence transcriptome datasets spanning 30 cell types, SenCID identifies six major senescence identities (SIDs). Different SIDs exhibit different senescence baselines, stemness, gene functions, and responses to senolytics...
April 8, 2024: Cell Metabolism
Manish Mishra, Judy Wu, Alice E Kane, Susan E Howlett
On average, aging is associated with unfavorable changes in cellular metabolism, which are the processes involved in the storage and expenditure of energy. However, metabolic dysregulation may not occur to the same extent in all older individuals as people age at different rates. Those who are aging rapidly are at increased risk of adverse health outcomes and are said to be "frail." Here, we explore the links between frailty and metabolism, including metabolic contributors and consequences of frailty. We examine how metabolic diseases may modify the degree of frailty in old age and suggest that frailty may predispose toward metabolic disease...
April 5, 2024: Cell Metabolism
Mingliang Zhao, Zhenxing Ren, Aihua Zhao, Yajun Tang, Junliang Kuang, Mengci Li, Tianlu Chen, Shouli Wang, Jieyi Wang, Huiheng Zhang, Jijun Wang, Tianhong Zhang, Jiahui Zeng, Xiaohua Liu, Guoxiang Xie, Penghong Liu, Ning Sun, Tianhao Bao, Tongtong Nie, Jingchao Lin, Ping Liu, Yuanyi Zheng, Xiaojiao Zheng, Tiemin Liu, Wei Jia
The gut-brain axis is implicated in depression development, yet its underlying mechanism remains unclear. We observed depleted gut bacterial species, including Bifidobacterium longum and Roseburia intestinalis, and the neurotransmitter homovanillic acid (HVA) in individuals with depression and mouse depression models. Although R. intestinalis does not directly produce HVA, it enhances B. longum abundance, leading to HVA generation. This highlights a synergistic interaction among gut microbiota in regulating intestinal neurotransmitter production...
April 3, 2024: Cell Metabolism
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