Article
Biochemistry & Molecular Biology
Marcelo V. Topete, Sara Andrade, Raquel L. Bernardino, Marta Guimaraes, Ana M. Pereira, Sofia B. Oliveira, Madalena M. Costa, Mario Nora, Mariana P. Monteiro, Sofia S. Pereira
Summary: Obesity is associated with changes in energy metabolism in adipose tissue. This study aimed to compare the energy metabolism and substrate preferences in visceral adipose tissue (VAT) between individuals with obesity class 2 and class 3. VAT from patients with obesity class 2 showed a higher dependence on glucose/pyruvate and glutamine metabolism, while VAT from patients with obesity class 3 had higher non-mitochondrial oxygen consumption. These findings suggest that patients with obesity class 2 may respond better to interventions targeting energy substrate modulation for obesity treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Hoyul Lee, Jae Han, Yu-Jeong Lee, Mi-Jin Kim, Woong Hee Kwon, Dipanjan Chanda, Themis Thoudam, Haushabhau S. Pagire, Suvarna H. Pagire, Jin Hee Ahn, Robert A. Harris, Eun Soo Kim, In-Kyu Lee
Summary: This study found that PDK4 expression increased during the development of colitis. Deletion of PDK4 from CD4(+) T cells can mitigate the development of colitis by modulating metabolism and calcium signaling. These findings suggest that PDK4 may be a potential therapeutic target for inflammatory bowel disease.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Qinfeng Li, Chao Li, Abdallah Elnwasany, Gaurav Sharma, Yu A. An, Guangyu Zhang, Waleed M. Elhelaly, Jun Lin, Yingchao Gong, Guihao Chen, Meihui Wang, Shangang Zhao, Chongshan Dai, Charles D. Smart, Juan Liu, Xiang Luo, Yingfeng Deng, Lin Tan, Shuang-Jie Lv, Shawn M. Davidson, Jason W. Locasale, Philip L. Lorenzi, Craig R. Malloy, Thomas G. Gillette, Matthew G. Vander Heiden, Philipp E. Scherer, Luke I. Szweda, Guosheng Fu, Zhao V. Wang
Summary: PKM1 plays a crucial role in maintaining a homeostatic response in the heart under hemodynamic stress, protecting against cardiac dysfunction and fibrosis caused by pressure overload. Furthermore, PKM1 is essential for enhancing glycolytic flux, mitochondrial respiration, and ATP production under pressure overload at a mechanistic level.
Article
Biotechnology & Applied Microbiology
Tao Si, Xuejian Ning, Hongwei Zhao, Mingmin Zhang, Ping Huang, Zhengguo Hu, Liu Yang, Lizhu Lin
Summary: The study found that miR-9-5p promotes proliferation, invasion, and migration of HCC cells by regulating the expression of PDK4, enhancing mitochondrial activity and energy metabolism, while suppressing apoptosis, ultimately increasing tumorigenicity in mouse xenograft models. This suggests that miR-9-5p and PDK4 could be potential therapeutic targets for preventing recurrence and metastasis of HCC.
CANCER GENE THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Nives Skorja Milic, Klemen Dolinar, Katarina Mis, Urska Matkovic, Marusa Bizjak, Mojca Pavlin, Matej Podbregar, Sergej Pirkmajer
Summary: Inhibition of pyruvate dehydrogenase kinase (PDK) by Dichloroacetate (DCA) can reduce the abundance of PDK isoenzymes in a cell-type-specific manner via both transcriptional and post-transcriptional mechanisms. The differential response of PDK isoenzymes to DCA in cancer cells and muscle cells highlights the importance of understanding the pharmacological effects of DCA in different cell types.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Nutrition & Dietetics
Song Hee Lee, Bo Young Choi, A. Ra Kho, Dae Ki Hong, Beom Seok Kang, Min Kyu Park, Si Hyun Lee, Hui Chul Choi, Hong Ki Song, Sang Won Suh
Summary: The combined treatment of pyruvate and DCA shows protective effects against seizure-induced hippocampal neuronal cell death by increasing the proportion of pyruvate converted to ATP.
Article
Biochemistry & Molecular Biology
Yudi Ma, Xiaohui Lai, Zhongling Wen, Ziling Zhou, Minkai Yang, Qingqing Chen, Xuan Wang, Feng Mei, Liu Yang, Tongming Yin, Shucun Sun, Guihua Lu, Jinliang Qi, Hongyan Lin, Hongwei Han, Yonghua Yang
Summary: The Warburg effect is essential for tumor proliferation, but reversing it can lead to a novel anti-cancer strategy. Two key enzymes in tumor glucose metabolism pathway, PKM2 and PDK1, not only contribute to the Warburg effect, but also serve as druggable targets for CRC. A series of benzenesulfonyl shikonin derivatives were designed to simultaneously regulate PKM2 and PDK1. Among them, compound Z10 acted as a PKM2 activator and PDK1 inhibitor, significantly inhibiting glycolysis and remodeling tumor metabolism. In addition, Z10 inhibited CRC cell proliferation and migration, and induced apoptosis. Furthermore, Z10 showed in vivo anti-tumor activity with lower toxicity compared to shikonin. Our findings suggest that altering tumor energy metabolism through multi-target synergies is feasible, and Z10 could be a potential anti-CRC agent.
BIOORGANIC CHEMISTRY
(2023)
Review
Medicine, Research & Experimental
Russel J. Reiter, Ramaswamy Sharma, Carmen Rodriguez, Vanesa Martin, Sergio Rosales-Corral, Debora Aparecida Pires de Campos Zuccari, Luiz Gustavo de Almeida Chuffa
Summary: This paper explores the relationship between endogenous melatonin and solid tumors, highlighting the potential of using melatonin to influence cancer cell metabolism. It suggests that solid tumors exhibit a healthier metabolic state at night, potentially reducing proliferation and invasiveness. The paper also proposes using melatonin in a time-sensitive treatment paradigm and combining it with traditional chemotherapy for improved outcomes in cancer treatment.
Article
Oncology
Esther P. Jane, Daniel R. Premkumar, Dhivyaa Rajasundaram, Swetha Thambireddy, Matthew C. Reslink, Sameer Agnihotri, Ian F. Pollack
Summary: This study demonstrates that targeting aurora kinases with tozasertib can effectively inhibit cell growth and migration in high-grade glioma cell lines, leading to cell death. However, sustained exposure to tozasertib can result in drug resistance, with upregulation of PDK genes playing a crucial role in the emergence of resistance.
MOLECULAR ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Mengjia Shen, Cankun Zheng, Lu Chen, Mingjue Li, Xiaoxia Huang, Mingyuan He, Chiyu Liu, Hairuo Lin, Wangjun Liao, Jianping Bin, Shiping Cao, Yulin Liao
Summary: LCZ696 can attenuate pressure overload-induced right ventricular remodeling by inhibiting PDK4, and PDK4 is a common therapeutic target for pressure overload-induced left ventricular and right ventricular remodeling.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Raquel Vaz, Josephine Wincent, Najla Elfissi, Kristina Rosengren Forsblad, Maria Pettersson, Karin Naess, Anna Wedell, Anna Wredenberg, Anna Lindstrand, Sofia Ygberg
Summary: This study reported a de novo heterozygous missense variant in the PDK1 gene in a girl with developmental delay and early onset severe epilepsy. Using a zebrafish model, the study showed the impact of this variant on energy metabolism and neuronal development, and the possible mechanism behind the clinical symptoms.
Article
Biochemistry & Molecular Biology
Jesus Fernandez-Felipe, Adrian Plaza, Gema Dominguez, Javier Perez-Castells, Victoria Cano, Francesco Cioni, Nuria Del Olmo, Mariano Ruiz-Gayo, Beatriz Merino
Summary: High-fat diets enriched with lauric acid do not increase leptin production and reduce the effect of leptin on kinase phosphorylation. Both high-fat diets affect adipocyte-size distribution and gene expression related to adipogenesis and inflammation. The composition of white adipose tissue is different between the two diets, which may impact the biophysical properties and signaling of leptin receptor.
Review
Endocrinology & Metabolism
Nicole K. H. Yiew, Brian N. Finck
Summary: Pyruvate metabolism plays a central role in carbon homeostasis and aberrant pyruvate metabolism is associated with various human metabolic disorders. The mitochondrial pyruvate carrier (MPC), composed of protein subunits MPC1 and MPC2, is involved in regulating the transport and metabolism of pyruvate, affecting multiple physiological processes. Understanding the mechanisms and processes regulated by pyruvate metabolism may lead to the development of novel therapeutic strategies.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Multidisciplinary Sciences
Yuko Katayama, Yayoi Kawata, Yusuke Moritoh, Masanori Watanabe
Summary: This study investigated the antidiabetic effect of PDK inhibition using DCA and found that it can effectively lower blood glucose levels, suggesting its potential value in the treatment of diabetes.
Article
Multidisciplinary Sciences
Alastair G. Kerr, Zuoneng Wang, Na Wang, Kelvin H. M. Kwok, Jutta Jalkanen, Alison Ludzki, Simon Lecoutre, Dominique Langin, Martin O. Bergo, Ingrid Dahlman, Carsten Mim, Peter Arner, Hui Gao
Summary: The study identifies ADIPINT, a human adipocyte-specific lncRNA, as a regulator of lipid metabolism in white adipocytes. ADIPINT interacts with pyruvate carboxylase and affects its abundance and enzymatic activity, which in turn influences adipocyte lipid synthesis and breakdown. ADIPINT expression is increased in obesity and is associated with adipose insulin resistance and pyruvate carboxylase activity.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Elise Saunier, Chantal Benelli, Sylvie Bortoli
INTERNATIONAL JOURNAL OF CANCER
(2016)
Article
Multidisciplinary Sciences
Kevin Hardonniere, Elise Saunier, Anthony Lemarie, Morgane Fernier, Isabelle Gallais, Cecile Helies-Toussaint, Baharia Mograbi, Samantha Antonio, Paule Benit, Pierre Rustin, Maxime Janin, Florence Habarou, Chris Ottolenghi, Marie-Therese Lavault, Chantal Benelli, Odile Sergent, Laurence Huc, Sylvie Bortoli, Dominique Lagadic-Gossmann
SCIENTIFIC REPORTS
(2016)
Article
Oncology
Ana A. Fernandez-Ramos, Catherine Marchetti-Laurent, Virginie Poindessous, Samantha Antonio, Pierre Laurent-Puig, Sylvie Bortoli, Marie-Anne Loriot, Nicolas Pallet
Article
Multidisciplinary Sciences
Kevin Hardonniere, Morgane Fernier, Isabelle Gallais, Baharia Mograbi, Normand Podechard, Eric Le Ferrec, Nathalie Grova, Brice Appenzeller, Agnes Burel, Martine Chevanne, Odile Sergent, Laurence Huc, Sylvie Bortoli, Dominique Lagadic-Gossmann
SCIENTIFIC REPORTS
(2017)
Article
Medicine, General & Internal
Paule Benit, Alice Pelhaitre, Elise Saunier, Sylvie Bortoli, Assetou Coulibaly, Malgorzata Rak, Manuel Schiff, Guido Kroemer, Massimo Zeviani, Pierre Rustin
Article
Oncology
Jean-Marc Blouin, Graziella Penot, Martine Collinet, Magali Nacfer, Claude Forest, Pierre Laurent-Puig, Xavier Coumoul, Robert Barouki, Chantal Benelli, Sylvie Bortoli
INTERNATIONAL JOURNAL OF CANCER
(2011)
Article
Multidisciplinary Sciences
Ana A. Fernandez-Ramos, Catherine Marchetti-Laurent, Virginie Poindessous, Samantha Antonio, Celine Petitgas, Irene Ceballos-Picot, Pierre Laurent-Puig, Sylvie Bortoli, Marie-Anne Loriot, Nicolas Pallet
SCIENTIFIC REPORTS
(2017)
Article
Multidisciplinary Sciences
Elise Saunier, Samantha Antonio, Anne Regazzetti, Nicolas Auzeil, Olivier Laprevote, Jerry W. Shay, Xavier Coumoul, Robert Barouki, Chantal Benelli, Laurence Huc, Sylvie Bortoli
SCIENTIFIC REPORTS
(2017)
Article
Environmental Sciences
Alix F. Leblanc, Eleonore A. Attignon, Emilie Distel, Spyros P. Karakitsios, Dimosthenis A. Sarigiannis, Sylvie Bortoli, Robert Barouki, Xavier Coumou, Martine Aggerbeck, Etienne B. Blanc
ENVIRONMENTAL RESEARCH
(2019)
Article
Multidisciplinary Sciences
Paule Benit, Agathe Kahn, Dominique Chretien, Sylvie Bortoli, Laurence Huc, Manuel Schiff, Anne-Paule Gimenez-Roqueplo, Judith Favier, Pierre Gressens, Malgorzata Rak, Pierre Rustin
Article
Environmental Sciences
Elias Zgheib, Min Ji Kim, Florence Jornod, Kevin Bernal, Celine Tomkiewicz, Sylvie Bortoli, Xavier Coumoul, Robert Barouki, Kelly De Jesus, Elise Grignard, Philippe Hubert, Efrosini S. Katsanou, Francois Busquet, Karine Audouze
Summary: Exposure to endocrine disrupting chemicals (EDCs) poses a significant public health threat, with a range of adverse health outcomes associated. The current regulatory tests do not cover all endocrine pathways, necessitating the search for more comprehensive testing methods for regulatory pre-validation. Through a combination of automated and manual screening, several non-validated experimental methods were identified, covering multiple endocrine pathways.
ENVIRONMENT INTERNATIONAL
(2021)
Article
Cell Biology
Carolina Duarte-Hospital, Arnaud Tete, Francois Brial, Louise Benoit, Meriem Koual, Celine Tomkiewicz, Min Ji Kim, Etienne B. Blanc, Xavier Coumoul, Sylvie Bortoli
Summary: Environmental factors have a significant impact on human health, including diet, sedentary lifestyle, and exposure to pollutants. The cellular and molecular events triggered by exposure to environmental pollutants vary greatly depending on age, chronicity, and exposure doses. Mitochondrial dysfunction is increasingly recognized as a major characteristic of environmental damage. This article reviews the multiple mechanisms by which pollutants cause mitochondrial toxicity in relation to chronic diseases and proposes the Aryl hydrocarbon Receptor (AhR) as an exposome receptor model that activates various toxic events through mitochondrial dysfunction. Finally, some remarks are provided on mitotoxicity and risk assessment.
Review
Environmental Sciences
Carolina Duarte Hospital, Arnaud Tete, Kloe Debizet, Jules Imler, Celine Tomkiewicz-Raulet, Etienne B. Blanc, Robert Barouki, Xavier Coumoul, Sylvie Bortoli
Summary: Succinate dehydrogenase inhibitors (SDHi) are fungicides used to control pathogenic fungi in crops. Recent studies show that these inhibitors may have toxic effects on non-target organisms, including humans, and their mechanism of carcinogenicity still needs further investigation.
ENVIRONMENT INTERNATIONAL
(2023)
Article
Nutrition & Dietetics
Carolina Duarte-Hospital, Laurence Huc, Sylvie Bortoli, Xavier Coumoul
CAHIERS DE NUTRITION ET DE DIETETIQUE
(2019)