Article
Biochemistry & Molecular Biology
Hui Ma, Jiayan Cui, Zehui Liu, Wenqing Fang, Sisi Lu, Shuying Cao, Yuanyuan Zhang, Ji-An Chen, Lixue Lu, Qiong Xie, Yonghui Wang, Ying Huang, Kongfei Li, Hongyan Tong, Jin Huang, Weiqiang Lu
Summary: This study demonstrates that induction of degradation of FLT3-ITD protein by DHODH blockade may offer a promising therapeutic strategy for AML patients harboring FLT3-ITD mutation.
Article
Neurosciences
Dongwook Kim, Hyeji Jung, Yoshinori Shirai, Hyeonho Kim, Jinhu Kim, Dongseok Lim, Takuma Mori, Hyojeong Lee, Dongseok Park, Hee Young Kim, Qi Guo, Bo Pang, Wen Qiu, Xueshan Cao, Emi Kouyama-Suzuki, Takeshi Uemura, Enas Kasem, Yu Fu, Seungjoon Kim, Akinori Tokunaga, Takahiro Yoshizawa, Tatsuo Suzuki, Hiroyuki Sakagami, Kea Joo Lee, Jaewon Ko, Katsuhiko Tabuchi, Ji Won Um
Summary: The study reveals the critical role of IQSEC3 in regulating synaptic inhibition in the hippocampal CA1 region for the formation of hippocampus-dependent fear memory. It mediates GABAergic synapse density and transmission and affects the maintenance of long-term potentiation. Additionally, abnormal activation of the S6K1 signaling pathway associated with IQSEC3 loss was also identified.
BIOLOGICAL PSYCHIATRY
(2022)
Article
Cell Biology
Sheikh Tahir Majeed, Asiya Batool, Rabiya Majeed, Nadiem Nazir Bhat, Muhammad Afzal Zargar, Khurshid Iqbal Andrabi
Summary: Phosphorylated S209-eIF4E interacts with the TOS motif of S6K1, releasing it from auto-inhibition and priming it for activation in an mTORC1-independent manner. The role of mTORC1 is limited to engaging eIF4E with the S6K1-TOS motif to influence S6K1's state of activation.
Article
Biochemistry & Molecular Biology
Ling Lin, Shumin Han, Zhihua Gong, Furong Ding, Zhonghua Liu, Wenjun Xiao
Summary: Extreme heat caused by global warming accelerated the frequency of heat stress. Proteotoxic stress induced by the aggregation of misfolded proteins and metabolic stress triggered by alterations in the metabolism were observed during heat stress. The activation of heat shock factor 1 (Hsf1) and its interaction with adenosine 5 '-monophosphate (AMP)-activated protein kinase (AMPK) are critical in addressing proteotoxicity and metabolic stress in heat-stressed organisms. Previous studies have shown that l-theanine (LTA) can regulate nutrient metabolism through the AMPK pathway and can alleviate heat stress. This study investigated the effects of LTA on nutrient metabolism in heat-stressed rats and characterized the underlying mechanisms using RNA sequencing and metabonomics. The results showed that LTA alleviated heat stress-induced liver damage, promoted body weight gain, decreased serum cortisol and enhanced the total protein content. Mechanistically, LTA alleviated heat stress-induced proteotoxic stress by acting on Hsf1/heat shock protein 70 (Hsp70) and promoted AMPK phosphorylation by suppressing Hsf1 expression, thus alleviating heat stress-induced metabolic stress.
Article
Biochemistry & Molecular Biology
Jian-Jun Jia, Roni M. Lahr, Michael T. Solgaard, Bruno J. Moraes, Roberta Pointet, An-Dao Yang, Giovanna Celucci, Tyson E. Graber, Huy-Dung Hoang, Marius R. Niklaus, Izabella A. Pena, Anne K. Hollensen, Ewan M. Smith, Malik Chaker-Margot, Leonie Anton, Christopher Dajadian, Mark Livingstone, Jaclyn Hearnden, Xu-Dong Wang, Yonghao Yu, Timm Maier, Christian K. Damgaard, Andrea J. Berman, Tommy Alain, Bruno D. Fonseca
Summary: The study reveals that mTORC1 controls TOP mRNA translation repression activity through phosphorylating LARP1, with some residues being especially sensitive to rapamycin. This phosphorylation affects the RNA-binding and translation inhibitory activities of LARP1, providing insights into a new model of translation control involving differentially regulated regions of LARP1.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Xiaoyue Ji, Junhong Chen, Chaoying You, Jing Sun, Xiulong Xu
Summary: Leflunomide controls obesity in part by activating AMPK and inducing lipophagy.
Article
Multidisciplinary Sciences
Douglas R. Wassarman, Kondalarao Bankapalli, Leo J. Pallanck, Kevan M. Shokat
Summary: Mammalian target of rapamycin (mTOR) is a crucial factor in cell growth and metabolism, and its signaling in different tissues affects whole-organism processes. Researchers have developed selecTOR, a chemical-genetic system that restricts the activity of rapamycin analog in specific cell populations, achieving selective mTOR inhibition.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Yuhan Yan, Chao Chen, Zhiguo Li, Jing Zhang, Narin Park, Cheng-Kui Qu
Summary: A continuous supply of exogenous arginine is crucial for the maintenance and function of normal hematopoietic stem cells (HSCs), but the L-arginine transporter CAT3 is dispensable for normal hematopoiesis and leukemogenesis.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Wayne A. Cabral, Urraca L. Tavarez, Indeevar Beeram, Diana Yeritsyan, Yoseph D. Boku, Michael A. Eckhaus, Ara Nazarian, Michael R. Erdos, Francis S. Collins
Summary: Hutchinson-Gilford progeria syndrome (HGPS) is a rare accelerated aging disorder characterized by cardiovascular disease and premature death, mostly caused by a single nucleotide mutation in the LMNA gene. A study using mice models carrying two copies of the BAC showed a more complete replication of HGPS phenotypic features in various tissues, and genetic reduction of mTOR extended the lifespan of these mice significantly, suggesting a potential treatment for HGPS through pharmacologic inhibition of the mTOR pathway.
Article
Chemistry, Medicinal
G. Leslie Burnett, Yu C. Yang, James B. Aggen, Jennifer Pitzen, Micah K. Gliedt, Chris M. Semko, Abby Marquez, James W. Evans, Gang Wang, Walter S. Won, Aidan C. A. Tomlinson, Gert Kiss, Christos Tzitzilonis, Arun P. Thottumkara, James Cregg, Kevin T. Mellem, Jong S. Choi, Julie C. Lee, Yongyuan Zhao, Bianca J. Lee, Justin G. Meyerowitz, John E. Knox, Jingjing Jiang, Zhican Wang, David Wildes, Zhengping Wang, Mallika Singh, Jacqueline A. M. Smith, Adrian L. Gill
Summary: Hyperactivation of mTOR kinase by mutations or crosstalk is common in tumors. We have developed a novel class of bi-steric inhibitors that target both orthosteric and allosteric binding sites, deepening the inhibition of mTORC1 while preserving selectivity for mTORC1 over mTORC2. In preclinical models, combination therapy of selective mTORC1 inhibition and covalent KRAS(G12C) inhibition showed increased antitumor activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Chun-hua Wang, Lu-kai Wang, Chang-chieh Wu, Mao-liang Chen, Chan-yen Kuo, Rong-yaun Shyu, Fu-ming Tsai
Summary: This study aimed to investigate the effects of TIG1 and mTOR signaling pathways associated with VAC14 on melanoma. The results showed that TIG1 was downregulated in malignant melanoma while VAC14 was upregulated. TIG1 inhibited the activation of mTOR signaling pathway by inhibiting VAC14, which may contribute to the prevention of malignant melanoma through retinoic acid via VAC14.
ANTICANCER RESEARCH
(2023)
Article
Multidisciplinary Sciences
Sebastien Soubeyrand, Paulina Lau, Kaitlyn Beehler, Kelsey McShane, Ruth McPherson
Summary: The study demonstrates that miR1908-5p affects metabolic and energy regulation in hepatocyte models through multiple pathways, including sensitivity to glucose, impact on autophagy and mitochondrial function, as well as decreased activation and/or levels of several key energy and metabolic regulators. This implicates miR1908-5p in metabolic and energy regulation in hepatocyte models.
SCIENTIFIC REPORTS
(2021)
Article
Immunology
Fang-Yi Yu, Kua Zheng, Yin-Fang Wu, Shen-Wei Gao, Qing-Yu Weng, Chen Zhu, Yan-Ping Wu, Miao Li, Zhong-Nan Qin, Jia-Fei Lou, Zhi-Hua Chen, Song -Min Ying, Hua-Hao Shen, Wen Li
Summary: Rapamycin exacerbates Staphylococcus aureus pneumonia by increasing the inflammatory levels of macrophages. Inhibition of the mTOR-RPS6 pathway upregulates the expression of cytokines and chemokines in macrophages, thereby promoting the infiltration of inflammatory cells and exacerbating tissue damage.
JOURNAL OF INFLAMMATION RESEARCH
(2023)
Article
Endocrinology & Metabolism
Calum Forteath, Ify Mordi, Raid Nisr, Erika J. Gutierrez-Lara, Noor Alqurashi, Iain R. Phair, Amy R. Cameron, Craig Beall, Ibrahim Bahr, Mohapradeep Mohan, Aaron K. F. Wong, Adel Dihoum, Anwar Mohammad, Colin N. A. Palmer, Douglas Lamont, Kei Sakamoto, Benoit Viollet, Marc Foretz, Chim C. Lang, Graham Rena
Summary: Using cellular approaches and proteomics, we found that metformin therapy for diabetes alters the regulation of branched chain amino acids through the suppression of the amino acid transporter SNAT2.
MOLECULAR METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Sudeep Gautam, Lisa Zhang, Cheol Lee, Irina Arnaoutova, Hung Dar Chen, Roberta Resaz, Alessandra Eva, Brian C. Mansfield, Janice Y. Chou
Summary: This study found that G6PT deficiency leads to impaired hepatic autophagy, which may be related to the development of HCA/HCC. Downregulation of SIRT1/FoxO3a and LKB1/AMPK signaling underlies impaired hepatic autophagy. Understanding this mechanism may guide future therapies.
HUMAN MOLECULAR GENETICS
(2022)
Article
Oncology
Yajing Gao, Pekka Paivinen, Sushil Tripathi, Eva Domenech-Moreno, Iris P. L. Wong, Kari Vaahtomeri, Ashwini S. Nagaraj, Sarang S. Talwelkar, Marc Foretz, Emmy W. Verschuren, Benoit Viollet, Yan Yan, Tomi P. Makela
Summary: This study reveals that in LKB1-mutant LUAD, inactivation of AMPK leads to immune evasion, attenuated antigen presentation, and the formation of an immune suppressive tumor microenvironment.
CLINICAL CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Annie Lee, Chandana Kondapalli, Daniel M. Virga, Tommy L. Lewis, So Yeon Koo, Archana Ashok, Georges Mairet-Coello, Sebastien Herzig, Marc Foretz, Benoit Viollet, Reuben Shaw, Andrew Sproul, Franck Polleux
Summary: This study reveals that soluble Amyloid-beta 1-42 oligomers (A beta 42o) trigger the loss of excitatory synapses in early Alzheimer's disease, prior to the formation of insoluble amyloid plaques. The researchers also found that A beta 42o leads to structural remodeling of mitochondria in specific regions and mediates synaptic loss through certain signaling pathways.
NATURE COMMUNICATIONS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Malgorzata Tokarska-Schlattner, Laurence Kay, Pascale Perret, Raffaella Isola, Stephane Attia, Frederic Lamarche, Cindy Tellier, Cecile Cottet-Rousselle, Amjad Uneisi, Isabelle Hininger-Favier, Marc Foretz, Herve Dubouchaud, Catherine Ghezzi, Christian Zuppinger, Benoit Viollet, Uwe Schlattner
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2022)
Article
Nutrition & Dietetics
Tristan Chalvon-Demersay, Claire Gaudichon, Joanna Moro, Patrick C. Even, Nadezda Khodorova, Julien Piedcoq, Benoit Viollet, Julien Averous, Anne-Catherine Maurin, Daniel Tome, Marc Foretz, Pierre Fafournoux, Dalila Azzout-Marniche
Summary: This study investigated the contribution of liver AMPK and GCN2 to the adaptation to high protein intake and found that they were not involved in this adaptation during the postprandial period.
EUROPEAN JOURNAL OF NUTRITION
(2023)
Article
Gastroenterology & Hepatology
Laurence Daoust, Beatrice S-Y Choi, Anne-Laure Agrinier, Thibault V. Varin, Adia Ouellette, Patricia L. Mitchell, Nolwenn Samson, Genevieve Pilon, Emile Levy, Yves Desjardins, Mathieu Laplante, Fernando F. Anhe, Vanessa P. Houde, Andre Marette
Summary: This study investigates the impact of housing conditions on the metabolic outcomes of germ-free (GF) mice after receiving faecal microbiota transplantation (FMT). The results reveal that the housing environment strongly influences gut microbiota composition and function, leading to distinctive phenotypes in recipient mice.
Article
Multidisciplinary Sciences
Javier Moral-Sanz, Sophronia A. Lewis, Sandy MacMillan, Marco Meloni, Heather McClafferty, Benoit Viollet, Marc Foretz, Jorge del-Pozo, A. Mark Evans
Summary: This study shows that deficiency of AMPK-alpha 1/alpha 2 in smooth muscles can cause persistent pulmonary hypertension in newborns. The findings provide important insights into the mechanism of pulmonary hypertension.
NATURE COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Iain R. Phair, Raid B. Nisr, Andrew J. M. Howden, Magdalena Sovakova, Noor Alqurashi, Marc Foretz, Douglas Lamont, Benoit Viollet, Graham Rena
Summary: This study demonstrates the integration of metabolite and kinase-based immunometabolic control in macrophages through the activation of AMP kinase. The deletion of AMPKa1 leads to a striking polarization of M1 macrophages upon LPS stimulation, along with increased expression of rate-limiting enzymes involved in various metabolic pathways.
MOLECULAR METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Sarah Lafleur, Antoine Bodein, Joanna Mbuya Malaika Mutombo, Alban Mathieu, Charles Joly Beauparlant, Xavier Minne, Fatiha Chandad, Arnaud Droit, Vanessa P. Houde
Summary: This study investigates the effects of a hyperglycemic microenvironment on host-microbiome interactions and host inflammatory response during periodontitis. It reveals the key variables, including genes, bacteria, and inflammatory cytokines, that contribute to periodontitis-induced inflammatory response in a hyperglycemic microenvironment. The findings shed light on the complex interrelationships involved in the regulation of periodontal inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Nutrition & Dietetics
Giselle S. Escouto, Gabriela Z. Port, Cristiane V. Tovo, Sabrina A. Fernandes, Alessandra Peres, Gilson P. Dorneles, Vanessa P. Houde, Thibault V. Varin, Genevieve Pilon, Andre Marette, Caroline Buss
Summary: This study evaluated the effects of probiotic supplementation on hepatic fibrosis, inflammatory markers, metabolic markers, and gut microbiota in NASH patients. The results showed that patients who received probiotic supplementation for 6 months had improved APRI scores, but no significant differences were observed in liver fibrosis, steatosis, inflammatory activity, and gut microbiota between the probiotic and placebo groups.
JOURNAL OF NUTRITION
(2023)
Review
Endocrinology & Metabolism
Marc Foretz, Bruno Guigas, Benoit Viollet
Summary: This Review presents the latest advances in understanding the mechanisms of action of metformin and discusses its potential repurposing for other indications. Metformin is currently the first-line medication for treating type 2 diabetes in most guidelines and is widely used by over 200 million patients. Its therapeutic action involves complex mechanisms that are not fully understood. Although the liver was initially identified as the main organ involved, increasing evidence suggests the involvement of other sites, including the gastrointestinal tract, gut microbial communities, and tissue-resident immune cells. The molecular mechanisms of metformin vary depending on the dose and duration of treatment, and recent studies have revealed a novel action on the lysosome surface at low concentrations. Considering its efficacy and safety in diabetes, attention has been given to using metformin as adjunct therapy for cancer, age-related diseases, inflammatory diseases, and COVID-19.
NATURE REVIEWS ENDOCRINOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Miroslava Kvandova, Sanela Rajlic, Paul Stamm, Isabella Schmal, Dominika Mihalikova, Marin Kuntic, Maria Teresa Bayo Jimenez, Omar Hahad, Marta Kollarova, Henning Ubbens, Lea Strohm, Katie Frenis, Georg Daniel Duerr, Marc Foretz, Benoit Viollet, Yue Ruan, Subao Jiang, Qi Tang, Hartmut Kleinert, Steffen Rapp, Adrian Gericke, Eberhard Schulz, Matthias Oelze, John F. Keaney, Andreas Daiber, Swenja Kroller-Schon, Thomas Jansen, Thomas Munzel
Summary: This study found that the activation of adenosine monophosphate-activated protein kinase (a1AMPK) through exercise, intermittent fasting, and pharmacological treatment effectively mitigates vascular dysfunction caused by aircraft noise. These findings provide a new approach for the prevention and treatment of transportation noise-associated diseases.
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
(2023)
Article
Multidisciplinary Sciences
Xavier Minne, Joanna Mbuya Malaika Mutombo, Fatiha Chandad, Roberto D. Fanganiello, Vanessa P. Houde
Summary: This study aimed to investigate the molecular mechanisms involved in the development and progression of periodontitis in an obesogenic microenvironment in response to periodontopathogens. The results showed that the combination of palmitate and Porphyromonas gingivalis enhanced the secretion of pro-inflammatory cytokines and affected genes involved in immune and inflammatory pathways. Therefore, systemic conditions, especially the obesogenic microenvironment, should be considered in the management of periodontal disease in obese patients.
Article
Multidisciplinary Sciences
Anne Garnier, Jerome Leroy, Claudine Delomenie, Philippe Mateo, Benoit Viollet, Vladimir Veksler, Mathias Mericskay, Renee Ventura-Clapier, Jerome Piquereau
Summary: The study explores the potential control of the beta-adrenergic pathway by AMP-activated protein kinase (AMPK) in the context of compromised energy metabolism. The activation of AMPK was found to down-regulate the expression of adenylyl cyclase 5 (AC5) and blunt the beta-adrenergic cascade, suggesting a compensatory energy sparing mechanism in dysfunctional myocardium.
Article
Gastroenterology & Hepatology
Pascale Gluais-Dagorn, Marc Foretz, Gregory R. Steinberg, Battsetseg Batchuluun, Anna Zawistowska-Deniziak, Joost M. Lambooij, Bruno Guigas, David Carling, Pierre-Axel Monternier, David E. Moller, Sebastien Bolze, Sophie Hallakou-Bozec
Summary: The study demonstrates that direct activation of AMPK can improve all core components of NASH and alleviate related hyperglycemia, dyslipidemia, and systemic inflammation. Additionally, novel properties of direct AMPK activation were revealed, including improved insulin resistance and direct suppression of inflammation and fibrogenesis. These findings suggest the potential for direct AMPK activation as an effective treatment for patients with NASH, with effects also observed in human cells.
HEPATOLOGY COMMUNICATIONS
(2022)