Article
Pharmacology & Pharmacy
Huiling Hu, Nannan Sun, Haiyan Du, Yuqing He, Kunyi Pan, Xiuli Liu, Xiaoxia Lu, Jie Wei, Mianmian Liao, Chaohui Duan
Summary: Previous studies have shown that PLZF plays a role in promoting gluconeogenic gene expression, hepatic glucose output, and consequent hyperglycemia. However, its role in regulating lipid metabolism was unknown. This study revealed that PLZF is an essential regulator of hepatic lipid and glucose metabolism. Overexpression of PLZF in the liver led to fatty liver, inflammation, impaired glucose tolerance, and insulin sensitivity. Knockdown of PLZF in obese mice alleviated hepatic steatosis. The underlying mechanism involved PLZF activating SREBP-1c gene transcription by binding to its promoter fragment, which depended on its interaction with SIRT1 to induce a repressor-to-activator conversion. These findings suggest that modulating PLZF expression in the liver could be a potential therapeutic approach for treating NAFLD.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Nal Ae Yoon, Sungho Jin, Jung Dae Kim, Zhong Wu Liu, Qiushi Sun, Rebecca Cardone, Richard Kibbey, Sabrina Diano
Summary: Lactate activates POMC neurons through redox signaling and blocking mitochondrial glucose utilization to regulate feeding and glucose metabolism.
Article
Multidisciplinary Sciences
Douglas L. Rothman, Stephen C. Stearns, Robert G. Shulman
Summary: Research indicates that during the Crabtree effect in yeast, short-term adaptation depends on the ability of the glycogen/trehalose shunt to balance the glycolytic pathway, with later gene expression of new isoforms of glycolytic enzymes providing additional homeostatic mechanisms for increased ATP production and product efficiency while maintaining glycolytic balance.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Khanh Van Doan, Le Trung Tran, Dong Joo Yang, Thu Thi Anh Ha, Thi Dang Mai, Seul Ki Kim, Ronald A. Depinho, Dong-Min Shin, Yun-Hee Choi, Ki Woo Kim
Summary: In this study, the essential role of hypothalamic astrocytic FoxO1 in maintaining normal neuronal activity in the hypothalamus and whole-body glucose metabolism was demonstrated. Inhibition of FoxO1 function in hypothalamic astrocytes alters cellular metabolism, enhancing astrocyte ATP production while decreasing lactate export. Specific deletion of astrocytic FoxO1, particularly in the hypothalamus, hyperactivates hypothalamic neuropeptide Y neurons, leading to increased feeding, impaired glucose regulation, diet-induced obesity, and systemic glucose dyshomeostasis.
Article
Neurosciences
Marco Tozzi, Erin L. Brown, Patricia S. S. Petersen, Morten Lundh, Marie S. Isidor, Kaja Plucinska, Thomas S. Nielsen, Marina Agueda-Oyarzabal, Lewin Small, Jonas T. Treebak, Brice Emanuelli
Summary: Afadin is a scaffold protein involved in insulin signaling and glucose metabolism, with its phosphorylation at S1795 being critical in metabolic tissues during obesity progression. Genetic silencing of Afadin(S1795) phosphorylation improves glucose homeostasis in the early stages of metabolic dysregulation. The dynamic regulation of Afadin abundance and phosphorylation during diet-induced obesity highlights its contribution to systemic insulin resistance and glucose intolerance.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Cell Biology
Jie Qi, Ying Lv, Ni-Er Zhong, Wen-Qi Han, Qi-Ling Gou, Chao-Feng Sun
Summary: This study investigates the molecular mechanisms behind glucose-induced foam cell formation. Through experiments and multi-omics analysis, it is discovered that high glucose accelerates lipid accumulation, reduces lipid efflux, and aggravates inflammation in macrophages. Glucose also alters the metabolic and transcriptional profiles of macrophages, disrupting key metabolic pathways and leading to the accumulation of pro-atherosclerotic lipids.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Liwen Ren, Jie Yi, Yihui Yang, Wan Li, Xiangjin Zheng, Jinyi Liu, Sha Li, Hong Yang, Yizhi Zhang, Binbin Ge, Sen Zhang, Weiqi Fu, Dexin Dong, Guanhua Du, Xifu Wang, Jinhua Wang
Summary: APOC1 is closely associated with immune cell infiltration in multiple cancers and primarily expressed in macrophages. It is significantly co-expressed with immune cell infiltration, immune checkpoints, MHC molecules, chemokines, and other immune-related genes. Experimental results suggest that APOC1 regulates macrophage polarization and promotes tumor metastasis in renal cell cancer.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Michele Yeo, Yong Chen, Changyu Jiang, Gang Chen, Kaiyuan Wang, Sharat Chandra, Andrey Bortsov, Maria Lioudyno, Qian Zeng, Peng Wang, Zilong Wang, Jorge Busciglio, Ru-Rong Ji, Wolfgang Liedtke
Summary: The study identifies a kinase-inhibitor, kenpaullone, as an enhancer of Kcc2 gene expression, which alleviates pain behavior in animal models and repairs neural-circuit disruption caused by elevated chloride levels. This compound was found to work by inhibiting GSK3ss and activating the Kcc2 promoter via KAISO transcription factor, offering a new approach to re-normalize disrupted inhibitory neurotransmission.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Luiz A. Dutra, Mariella G. Lacerda, Maiara Destro Inacio, Johnny W. L. Martins, Ana C. Lopes Silva, Patricia Bento da Silva, Marlus Chorilli, Angelica A. Amato, Amanda M. Baviera, Marisa Passarelli, Rafael V. C. Guido, Jean L. Dos Santos
Summary: Peroxisome proliferator-activated receptors (PPARs) are potential therapeutic targets for metabolic diseases, and this study focuses on the design and synthesis of stilbene-based compounds as dual PPAR alpha/gamma partial agonists. The lead compound 5b showed promising effects in removing cholesterol from foam cells and improving lipid levels, insulin sensitivity, and glucose levels in an obesity mouse model.
BIOORGANIC CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Annabella F. Thomas, Gemma L. Kelly, Andreas Strasser
Summary: TP53 is a crucial tumor suppressor that regulates various cellular processes to prevent tumorigenesis, including cell death, cell cycle, cell senescence, DNA repair, and metabolism. Mutations in the TP53 gene are commonly found in human cancers and are associated with poor responses to therapy. However, the mechanism by which TP53 suppresses tumors involves more than just inducing apoptotic cell death, as mice lacking critical effectors of TP53-induced apoptosis or cell cycle arrest and senescence do not spontaneously develop tumors.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Multidisciplinary Sciences
Akira Terakawa, Yanhui Hu, Toshiya Kokaji, Katsuyuki Yugi, Keigo Morita, Satoshi Ohno, Yifei Pan, Yunfan Bai, Andrey A. Parkhitko, Xiaochun Ni, John M. Asara, Martha L. Bulyk, Norbert Perrimon, Shinya Kuroda
Summary: This study constructed a transgenic network to investigate the role of insulin in Drosophila cells. The findings suggest that insulin promotes cell growth and proliferation by regulating gene expression, especially genes involved in anabolic metabolism.
Article
Immunology
Zhilin Peng, Yiwen Zhang, Xiancai Ma, Mo Zhou, Shiyu Wu, Zheng Song, Yaochang Yuan, Yingshi Chen, Yuzhuang Li, Guanwen Wang, Feng Huang, Yidan Qiao, Baijing Xia, Weiwei Liu, Jun Liu, Xu Zhang, Xin He, Ting Pan, Hanshi Xu, Hui Zhang
Summary: The study highlights the significant role of Brd4 in regulating glucose metabolism and maintaining receptor expression in CD8(+) T cells' homeostasis and immune response.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yafang Wang, Na Li, Xin Zhang, Tiffany Horng
Summary: Mitochondria play a crucial role in regulating the activation, differentiation, and survival of macrophages and other immune cells. Changes in mitochondrial metabolism and various metabolites coordinate macrophage activation to distinct cellular states, clarifying the essential link between mitochondrial metabolism and immunity. Additionally, mitochondrial dysfunction and oxidative stress contribute to dysregulation of the inflammatory response in disease settings.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Rui Shao, Xinmeng Liao, Yawen Lan, Hui Zhang, Lin Jiao, Qingyang Du, Dong Han, Qinghui Ai, Kangsen Mai, Min Wan
Summary: The study demonstrated that 1,25(OH)(2)D-3 enhances insulin signaling pathway and glucose homeostasis in zebrafish by activating VDRE in the promoter region of insra.
Article
Genetics & Heredity
Yanhua Chen, Xiaomeng Du, Annapurna Kuppa, Mary F. Feitosa, Lawrence F. Bielak, Jeffrey R. O'Connell, Solomon K. Musani, Xiuqing Guo, Bratati Kahali, Vincent L. Chen, Albert V. Smith, Kathleen A. Ryan, Gudny Eirksdottir, Matthew A. Allison, Donald W. Bowden, Matthew J. Budoff, John Jeffrey Carr, Yii-Der I. Chen, Kent D. Taylor, Antonino Oliveri, Adolfo Correa, Breland F. Crudup, Sharon L. R. Kardia, Thomas H. Mosley, Jill M. Norris, James G. Terry, Jerome I. Rotter, Lynne E. Wagenknecht, Brian D. Halligan, Kendra A. Young, John E. Hokanson, George R. Washko, Vilmundur Gudnason, Michael A. Province, Patricia A. Peyser, Nicholette D. Palmer, Elizabeth K. Speliotes
Summary: This study conducted a genome-wide association analysis to identify risk loci for nonalcoholic fatty liver disease (NAFLD) and found possible biological pathways contributing to the development of the disease. The study also discovered at least seven subtypes of NAFLD and revealed that individuals with higher genetic risk are at a greater risk of developing NAFLD, cirrhosis, and hepatocellular carcinoma.
Article
Multidisciplinary Sciences
Elena M. Pugacheva, Naoki Kubo, Dmitri Loukinov, Md Tajmul, Sungyun Kang, Alexander L. Kovalchuk, Alexander V. Strunnikov, Gabriel E. Zentner, Bing Ren, Victor V. Lobanenkov
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biology
Kenneth T. Farabaugh, Dawid Krokowski, Bo-Jhih Guan, Zhaofeng Gao, Xing-Huang Gao, Jing Wu, Raul Jobava, Greeshma Ray, Tristan J. de Jesus, Massimiliano G. Bianchi, Evelyn Chukwurah, Ovidio Bussolati, Michael Kilberg, David A. Buchner, Ganes C. Sen, Calvin Cotton, Christine McDonald, Michelle Longworth, Parameswaran Ramakrishnan, Maria Hatzoglou
Article
Biochemistry & Molecular Biology
Robert A. Policastro, R. Taylor Raborn, Volker P. Brendel, Gabriel E. Zentner
Article
Genetics & Heredity
Lina Hamad, Khalil Kreidieh, Ghunwa Nakouzi, Elaine Lyon, Soha Yazbek
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2020)
Article
Genetics & Heredity
Anna K. Miller, Anlu Chen, Jacquelaine Bartlett, Li Wang, Scott M. Williams, David A. Buchner
G3-GENES GENOMES GENETICS
(2020)
Article
Genetics & Heredity
Jason P. Tourigny, Kenny Schumacher, Moustafa M. Saleh, Didier Devys, Gabriel E. Zentner
Summary: In the yeast Saccharomyces cerevisiae, the architectural subunits Med14 and Med17 of the Mediator complex are essential for transcription, with Med17 playing a more significant role. Both Med14 and Med17 are crucial for preinitiation complex assembly and transcription, but the head module, particularly Med17, is the key functional module of Mediator in this regard.
Article
Cell Biology
Alyssa Charrier, Xuan Xu, Bo-Jhih Guan, Justine Ngo, Anthony Wynshaw-Boris, Maria Hatzoglou, David A. Buchner
Summary: This study revealed the crucial role of ZFP407 in regulating PPAR-γ in adipocytes, and its expression in adipogenesis and tissues is associated with lipodystrophy and insulin resistance.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Multidisciplinary Sciences
Kevin A. Murach, Bailey D. Peck, Robert A. Policastro, Ivan J. Vechetti, Douglas W. Van Pelt, Cory M. Dungan, Lance T. Denes, Xu Fu, Camille R. Brightwell, Gabriel E. Zentner, Esther E. Dupont-Versteegden, Christopher Richards, Jeramiah J. Smith, Christopher S. Fry, John J. McCarthy, Charlotte A. Peterson
Summary: The study demonstrates that satellite cells communicate with other cells in skeletal muscle during mechanical overload, affecting proper long-term extracellular matrix deposition. They modulate chemokine gene expression and influence cell phenotype through extracellular vesicle delivery of miR-206.
Article
Oncology
Samuel A. Miller, Robert A. Policastro, Shruthi Sriramkumar, Tim Lai, Thomas D. Huntington, Christopher A. Ladaika, Daeho Kim, Chunhai Hao, Gabriel E. Zentner, Heather M. O'Hagan
Summary: In BRAF-mutant colorectal cancer, EEC progenitor cells are enriched and blocked from further differentiation by DNA methylation and NEUROD1 gene silencing. Secretory cells and factors they secrete promote colony formation and cell survival pathways, and can be suppressed by LSD1 inhibition. These findings highlight the important role of EEC progenitors in supporting colorectal cancer progression.
Article
Cell Biology
Lina Acevedo Rua, Marcus Mumme, Cristina Manferdini, Salim Darwiche, Ahmad Khalil, Morgane Hilpert, David A. Buchner, Gina Lisignoli, Paola Occhetta, Brigitte von Rechenberg, Martin Haug, Dirk J. Schaefer, Marcel Jakob, Arnold Caplan, Ivan Martin, Andrea Barbero, Karoliina Pelttari
Summary: N-TEC can maintain cartilaginous properties, alter the inflammatory profile of cells in osteoarthritic joints, and survive engraftment in mouse and sheep models. Clinical trials on two OA patients showed safety and efficacy, with reduced pain and improved joint function reported after 14 months.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Genetics & Heredity
Moustafa M. Saleh, Celia Jeronimo, Francois Robert, Gabriel E. Zentner
Summary: The Mediator coactivator complex is divided into four modules, with deletion of Med16 affecting genes dependent on the SAGA complex and TFIID complex. Altering the balance of transcription pre-initiation complex formation can partially restore normal transcription activity.
Article
Genetics & Heredity
Moustafa M. Saleh, Heather A. Hundley, Gabriel E. Zentner
Summary: Regulation of RNA polymerase II transcription involves the concerted efforts of several multisubunit coactivator complexes, which interact with the RNA polymerase II preinitiation complex to stimulate transcription. Our study shows that separation of the Mediator core from Mediator's tail module leads to overactivation of genes dependent on TFIID for expression, which can be suppressed by disruption of the Spt-Ada-Gcn5-Acetyl transferase complex. Furthermore, we observed that depletion of the essential TFIID subunit Taf13 can suppress the overactivation of these genes when Med16 is simultaneously removed.
G3-GENES GENOMES GENETICS
(2022)
Review
Biochemical Research Methods
Robert A. Policastro, Gabriel E. Zentner
Summary: TSS selection plays a critical role in transcript stability, translation, and protein sequence, contributing significantly to transcript isoform diversity in humans and playing a role in various human diseases, including cancer. A wide range of techniques have been used to profile TSSs globally, providing insights into gene regulation and promising future prospects in this field of study.
CELL REPORTS METHODS
(2021)
Article
Genetics & Heredity
Robert A. Policastro, Daniel J. McDonald, Volker P. Brendel, Gabriel E. Zentner
Summary: This study highlights the impact of heterogeneity in transcription initiation on transcript stability and translation, and the application of sequencing methods like STRIPE-seq in global TSS profiling. The development of TSRexploreR for end-to-end TSS mapping data analysis and its various functions for promoter atlas construction and differential gene expression studies are discussed.
NAR GENOMICS AND BIOINFORMATICS
(2021)
Review
Public, Environmental & Occupational Health
Lina Hamad, Khalil Kreidieh, Mirna Bou Hamdan, Ghunwa Nakouzi, Soha Yazbek
JOURNAL OF IMMIGRANT AND MINORITY HEALTH
(2020)