Article
Chemistry, Medicinal
Yongjun Zang, Luyang Tai, Yuanyang Hu, Yu Wang, Hongbin Sun, Xiaoan Wen, Haoliang Yuan, Liang Dai
Summary: A novel macrocyclic compound 2 with potent ACLY inhibitory activity and improved metabolic stability has been identified, highlighting its potential as a lead compound worthy of further study.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Immunology
Sanne G. S. Verberk, Hendrik J. P. van der Zande, Jeroen Baardman, Kyra E. de Goede, Karl J. Harber, Eelco D. Keuning, Joost M. Lambooij, Frank Otto, Anna Zawistowska-Deniziak, Helga E. de Vries, Menno P. J. de Winther, Bruno Guigas, Jan Van den Bossche
Summary: Research indicates that despite enhanced inflammatory responses in vitro, deficiency of macrophage Acly does not worsen acute and chronic inflammatory responses in vivo. Myeloid-specific Acly deletion has limited impact on inflammation and overall metabolic homeostasis in inflammatory disorders like multiple sclerosis and obesity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Meng Zhang, Ruyi Peng, Haizhou Wang, Zhenwei Yang, Hailin Zhang, Yangyang Zhang, Meng Wang, Hongling Wang, Jun Lin, Qiu Zhao, Jing Liu
Summary: This study discovered that Nanog can induce cellular dormancy in colorectal cancer cells through the FAO/ACLY-dependent pathway. This finding reveals a specific mechanism governing cellular dormancy in colorectal cancer.
CELL DEATH & DISEASE
(2022)
Article
Immunology
Monica Dominguez, Verena Truemper, Ana Carolina Mota, Bernhard Bruene, Dmitry Namgaladze
Summary: ATP-citrate lyase (ACLY) is a key enzyme involved in metabolic and epigenetic gene regulation. This study investigated the impact of ACLY phosphorylation on its function in human myeloid cells and found that phosphorylation at serine 455 does not affect the enzymatic activity of ACLY. Additionally, loss of ACLY activity may trigger long-term adaptive mechanisms that increase inflammatory responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Endocrinology & Metabolism
Zishun Zhan, Aimei Li, Wei Zhang, Xueqin Wu, Jinrong He, Zhi Li, Yanchun Li, Jian Sun, Hao Zhang
Summary: We evaluated a novel treatment for obesity-related renal issues by using an ATP-citrate lyase (ACL) inhibitor to reduce ectopic lipid accumulation in the kidney and the resulting inflammation. The results showed that the ACL inhibitor BMS-303141 had the highest affinity for ACL and could decrease ACL expression in the kidneys of db/db mice, leading to a reduction in renal ectopic lipid accumulation. Moreover, reducing ectopic lipid accumulation also improved renal injuries, inflammation, and tubulointerstitial fibrosis.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Medicine, Research & Experimental
Mohamed M. Elseweidy, Alaa S. Elawady, Mohammed S. Sobh, Gehad M. Elnagar
Summary: The study aimed to investigate the metabolic effects of lycopene (LYC) and atorvastatin (ATOR) in a diabetic hyperlipidemic rat model. The results showed that LYC had better effects on the studied biomarkers, indicating its potential as a natural therapeutic agent for hyperlipidemia.
Review
Immunology
Monica Dominguez, Bernhard Bruene, Dmitry Namgaladze
Summary: Recent studies have shown the profound influence of metabolism on immune responses, particularly through epigenetic regulation of gene expression. ACLY plays a crucial role in the formation of cytosolic acetyl-CoA, supporting de novo lipogenesis and contributing to epigenetic regulation through histone acetylation. Alternative sources of acetyl-CoA also play a role in metabolic and epigenetic regulation in immune cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Yuan Yao, Jiaming Shi, Chunlai Zhang, Wei Gao, Ning Huang, Yaobei Liu, Weiwen Yan, Yingguang Han, Wenjuan Zhou, Liang Kong
Summary: Hyperglycemia-induced aberrant glucose metabolism is a causative factor of neurodegeneration and cognitive impairment in diabetes mellitus (DM) patients. The pyruvate dehydrogenase kinase (PDK)-lactic acid axis and histone acetylation modification play important roles in the regulation of PDK1 expression under high glucose conditions. Overexpression of PDK1 can protect against hyperglycemia-induced neuronal injury and cognitive impairment in diabetic mice.
CELL DEATH & DISEASE
(2023)
Article
Medicine, Research & Experimental
Christoph Trautwein, Laimdota Zizmare, Irina Maurer, Benjamin Bender, Bjorn Bayer, Ulrike Ernemann, Marcos Tatagiba, Stefan J. Grau, Bernd J. Pichler, Marco Skardelly, Ghazaleh Tabatabai
Summary: This study presents a valuable resource for analyzing tissue metabolites in diffuse glioma patients, revealing the modulations of metabolites by IDH1 mutation, histology, and tumor treatments. Furthermore, tissue metabolites were found to correlate with patient survival, potentially serving as prognostic and surrogate biomarkers in future clinical studies.
Article
Multidisciplinary Sciences
Qiang Chen, Jianlong Du, Kun Cui, Wei Fang, Zengqi Zhao, Qiuchi Chen, Kangsen Mai, Qinghui Ai
Summary: Acetylation plays a key role in regulating inflammation induced by lipid surplus, with studies showing that high-fat diet can enhance mitochondrial fatty acid beta-oxidation and increase acetyl-CoA levels in the liver. Activation of ACLY and CEP leads to heightened p65 acetylation, exacerbating inflammation, while inactivation of SIRT1 further intensifies the inflammatory response.
Article
Medicine, Research & Experimental
Mohamed M. Elseweidy, Ahmed E. Elesawy, Mohammed S. Sobh, Gehad M. Elnagar
Summary: High-fructose intake can induce non-alcoholic fatty liver disease (NAFLD) and hyperuricemia. Ellagic acid can alleviate these conditions through the activation of CTRP3 and inhibition of ACL activities, showing more remarkable effects than allopurinol.
Article
Medicine, General & Internal
Rebecca D. D. Ganetzky, Andrew L. L. Markhard, Irene Yee, Sheila Clever, Alan Cahill, Hardik Shah, Zenon Grabarek, Tsz-Leung To, Vamsi K. K. Mootha
Summary: This is a case study of identical twin boys who had low body weight despite excessive caloric intake, which was attributed to a dominant mitochondrial uncoupling syndrome with hypermetabolism.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Plant Sciences
Kaili Ren, Weiping Kong, Taoxia Tang, Hong Cheng
Summary: In this study, the structure and phylogenetics of CmACL genes in melon were analyzed, and their important roles in sugar and acid accumulation were demonstrated. Four CmACL genes were identified and members within the same subfamily shared similar biological functions. The CmACL proteins were closely related to tricarboxylic acid cycle, glyoxylic acid cycle, and glycolytic pathway, indicating their involvement in sugar and acid metabolism.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Oncology
Kyra E. de Goede, Sanne G. S. Verberk, Jeroen Baardman, Karl J. Harber, Yvette van Kooyk, Menno P. J. de Winther, Sjoerd T. T. Schetters, Jan Van den Bossche
Summary: Targeting ATP-citrate lyase (Acly) as a therapy for cancer does not have adverse effects on tumor-associated macrophages (TAMs), while Acly-deficient TAMs do not impact tumor growth.
Article
Biochemistry & Molecular Biology
Ying Zhan, Wei Qiao, Bolong Yi, Xinyu Yang, Miaomiao Li, Lu Sun, Lian Ji, Peng Su, Xin Wang, Furong Zhang, Rui Zhang, Mingjun Gao, Wujun Zhao, Yichen Song
Summary: This study found that TMEM198B promotes the malignant progression of glioma by regulating lipid metabolism reprogramming and remodeling immune microenvironment. TMEM198B increases PLAGL2 expression, which activates ACLY and ELOVL6, influencing the behavior of glioma cells. Additionally, TMEM198B promotes M2 polarization of macrophages via glioma-derived exosomes, further facilitating immune escape of glioma cells.
Article
Pharmacology & Pharmacy
Magdalena Koziczak-Holbro, Dean F. Rigel, Berengere Dumotier, David A. Sykes, Jeffrey Tsao, Ngoc-Hong Nguyen, Julian Bosch, Marie Jourdain, Ludivine Flotte, Yuichiro Adachi, Michael Kiffe, Moise Azria, Robin A. Fairhurst, Steven J. Charlton, Brian P. Richardson, Estelle Lach-Trifilieff, David J. Glass, Thomas Ullrich, Shinji Hatakeyama
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2019)
Article
Cell Biology
Jason D. Roh, Ryan Hobson, Vinita Chaudhari, Pablo Quintero, Ashish Yeri, Mark Benson, Chunyang Xiao, Daniel Zlotoff, Vassilios Bezzerides, Nicholas Houstis, Colin Platt, Federico Damilano, Brian R. Lindman, Sammy Elmariah, Michael Biersmith, Se-Jin Lee, Christine E. Seidman, Jonathan G. Seidman, Robert E. Gerszten, Estelle Lach-Trifilieff, David J. Glass, Anthony Rosenzweig
SCIENCE TRANSLATIONAL MEDICINE
(2019)
Article
Biochemistry & Molecular Biology
Giselle A. Joseph, Sharon X. Wang, Cody E. Jacobs, Weihua Zhou, Garrett C. Kimble, Herman W. Tse, John K. Eash, Tea Shavlakadze, David J. Glass
MOLECULAR AND CELLULAR BIOLOGY
(2019)
Article
Multidisciplinary Sciences
Perrine Castets, Nathalie Rion, Marine Theodore, Denis Falcetta, Shuo Lin, Markus Reischl, Franziska Wild, Laurent Guerard, Christopher Eickhorst, Marielle Brockhoff, Maitea Guridi, Chikwendu Ibebunjo, Joseph Cruz, Michael Sinnreich, Ruediger Rudolf, David J. Glass, Markus A. Ruegg
NATURE COMMUNICATIONS
(2019)
Article
Multidisciplinary Sciences
Samuel M. Cadena, Yunyu Zhang, Jian Fang, Sophie Brachat, Pia Kuss, Elisa Giorgetti, Louis S. Stodieck, Michaela Kneissel, David J. Glass
SCIENTIFIC REPORTS
(2019)
Article
Cell Biology
Paola Sebastiani, Stefano Monti, Melody Morris, Anastasia Gurinovich, Tanaka Toshiko, Stacy L. Andersen, Benjamin Sweigar, Luigi Ferrucci, Lori L. Jennings, David J. Glass, Thomas T. Perls
Article
Cell Biology
Tea Shavlakadze, Melody Morris, Jian Fang, Sharon X. Wang, Jiang Zhu, Weihua Zhou, Herman W. Tse, Ricardo Mondragon-Gonzalez, Guglielmo Roma, David J. Glass
Article
Cell Biology
Ajeet Pratap Singh, Maria X. Sosa, Jian Fang, Shiva Kumar Shanmukhappa, Alexis Hubaud, Caroline H. Fawcett, Gregory J. Molind, Tingwei Tsai, Paola Capodieci, Kristie Wetzel, Ellen Sanchez, Guangliang Wang, Matthew Coble, Wenlong Tang, Samuel M. Cadena, Mark C. Fishman, David J. Glass
Article
Cell Biology
Liqing Luo, Sherry C. Martin, Jascha Parkington, Samuel M. Cadena, Jiang Zhu, Chikwendu Ibebunjo, Serge Summermatter, Nicole Londraville, Krystyna Patora-Komisarska, Leo Widler, Huili Zhai, Anne-Ulrike Trendelenburg, David J. Glass, Jun Shi
Article
Cell Biology
Paola Sebastiani, Anthony Federico, Melody Morris, Anastasia Gurinovich, Toshiko Tanaka, Kevin B. Chandler, Stacy L. Andersen, Gerald Denis, Katherine Costello, Luigi Ferrucci, Lori Jennings, David J. Glass, Stefano Monti, Thomas T. Perls
Summary: Using samples from the New England Centenarian Study, researchers characterized the serum proteome of centenarians, their offspring, and age-matched controls. They identified protein signatures associated with longer survival in centenarians and younger individuals and found similarities in aging markers between centenarians and short-lived cohorts. The study provides specific circulating biomarkers of healthy aging and longevity, suggesting potential mechanisms to prolong health and support longevity.
Article
Geriatrics & Gerontology
Anastasia Gurinovich, Zeyuan Song, William Zhang, Anthony Federico, Stefano Monti, Stacy L. Andersen, Lori L. Jennings, David J. Glass, Nir Barzilai, Sofiya Millman, Thomas T. Perls, Paola Sebastiani
Summary: The study conducted a genome-wide association study and proteomic analysis on centenarians and controls, identifying genetic variants and protein signatures associated with longevity. The findings suggest that these features could be potential targets for discovering healthy-aging interventions.
Article
Biology
Marco S. Kaiser, Giulia Milan, Daniel J. Ham, Shuo Lin, Filippo Oliveri, Kathrin Chojnowska, Lionel A. Tintignac, Nitish Mittal, Christian E. Zimmerli, David J. Glass, Mihaela Zavolan, Markus A. Rueegg
Summary: Muscle size is regulated by the PI3K-PKB/Akt-mTORC1-FoxO pathway, which controls protein synthesis and breakdown. Paradoxically, while mTORC1 activity is necessary for muscle hypertrophy, its constant activation promotes protein breakdown through the UPS. This study highlights the importance of mTORC1-mediated PKB/Akt inhibition and the role of the UPS in muscle atrophy and proteome integrity.
COMMUNICATIONS BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Michael D. Kessler, Amy Damask, Sean O'Keeffe, Nilanjana Banerjee, Dadong Li, Kyoko Watanabe, Anthony Marketta, Michael Van Meter, Stefan Semrau, Julie Horowitz, Jing Tang, Jack A. Kosmicki, Veera M. Rajagopal, Yuxin Zou, Yariv Houvras, Arkopravo Ghosh, Christopher Gillies, Joelle Mbatchou, Ryan R. White, Niek Verweij, Jonas Bovijn, Neelroop N. Parikshak, Michelle G. LeBlanc, Marcus Jones, David J. Glass, Luca A. Lotta, Michael N. Cantor, Gurinder S. Atwal, Adam E. Locke, Manuel A. R. Ferreira, Raquel Deering, Charles Paulding, Alan R. Shuldiner, Gavin Thurston, Adolfo A. Ferrando, Will Salerno, Jeffrey G. Reid, John D. Overton, Jonathan Marchini, Hyun M. Kang, Aris Baras, Goncalo R. Abecasis, Eric Jorgenson
Summary: Clonal haematopoiesis, associated with ageing and adverse health outcomes, involves the expansion of certain blood cell lineages. This study identified novel germline genetic variations influencing predisposition to clonal haematopoiesis using exome sequence data from over 600,000 individuals. The study also found associations between clonal haematopoiesis and severe COVID-19 outcomes, cardiovascular disease, and malignancy.
Article
Biochemistry & Molecular Biology
Megan McAleavy, Qian Zhang, Peter J. Ehmann, Jianing Xu, Matthew F. Wipperman, Dharani Ajithdoss, Li Pan, Matthew Wakai, Raphael Simonson, Abhilash Gadi, Adelekan Oyejide, Sara C. Hamon, Anita Boyapati, Lori G. Morton, Tea Shavlakadze, Christos A. Kyratsous, David J. Glass
Summary: Patients with elevated activin A, activin B, and FLRG at hospital admission are associated with severe outcomes of COVID-19. Inhibition of activin A signaling may be beneficial in treating COVID-19 patients with ARDS.
MOLECULAR AND CELLULAR BIOLOGY
(2022)
Correction
Medicine, Research & Experimental
Hui-Hua Li, Monte S. Willis, Pamela Lockyer, Nathaniel Miller, Holly McDonough, David J. Glass, Cam Patterson
JOURNAL OF CLINICAL INVESTIGATION
(2022)