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Metabolites
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Manipulation of Metabolic Pathways by Transcription Factors
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Manipulation of Metabolic Pathways by Transcription Factors

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Cell Metabolism".

Deadline for manuscript submissions: closed (1 March 2023) | Viewed by 7458

Special Issue Editor

Dr. JooMan Park

E-Mail Website
Guest Editor
Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60607, USA
Interests: glucose metabolism; lipid metabolism; obesity; type 2 diabetes; aging; transcription factors; secretion factors

Special Issue Information

Dear Colleagues,

With the technological improvement of metabolomics approaches over the past decade, transcription factors are successfully being used to understand the dynamic responses in biochemical metabolic research. Transcription factors typically consist of a repressor or activator protein regulating the transcriptional activity of a specific promoter within almost all cells. Transcription factors interact with biomolecule (metabolites) though direct and indirect cooperative mechanisms. However, there are relatively few studies describing how transcription factors are closely connected with metabolites for the regulation of metabolic pathways. Therefore, the function of metabolites and transcription factors in human chronic metabolic diseases such as obesity, diabetes, cancer, and cardiovascular diseases needs further study. This Special Issue will provide a forum for the presentation of research findings related to the modulation of metabolism by transcription factors. It aims to highlight advances in the field.

Dr. JooMan Park
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glucose metabolism
  • lipid metabolism
  • cancer metabolism
  • cardiovascular diseases
  • transcription factors
  • gene expression
  • enhancer and repressor
  • metabolites

Published Papers (4 papers)

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Research

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20 pages, 4819 KiB  
Article
Understanding Transcription Factors and How They Affect Processes in Cucumber Sex Determination
by Szymon Turek, Aparna, Agnieszka Skarzyńska, Wojciech Pląder and Magdalena Pawełkowicz
Metabolites 2023, 13(6), 740; https://doi.org/10.3390/metabo13060740 - 10 Jun 2023
Cited by 2 | Viewed by 1102
Abstract
Plant reproduction is a fundamental process on Earth from the perspective of biodiversity, biomass gain, and crop productivity. It is therefore important to understand the sex determination process, and many researchers are investigating the molecular basis of this phenomenon. However, information on the [...] Read more.
Plant reproduction is a fundamental process on Earth from the perspective of biodiversity, biomass gain, and crop productivity. It is therefore important to understand the sex determination process, and many researchers are investigating the molecular basis of this phenomenon. However, information on the influence of transcription factors (TFs), genes that encode DNA-binding proteins, on this process is limited, although cucumber is a model plant in this regard. In the present study, based on RNA-seq data for differentially expressed genes (DEGs), we aimed to investigate the regulatory TFs that may influence the metabolic processes in the shoot apex containing the forming flower buds. Therefore, the annotation of the genome of the B10 cucumber line was supplemented with the assigned families of transcription factors. By performing ontology analyses of the DEGs, the processes they participate in were identified, and TFs were located among the results. In addition, TFs that have significantly overrepresented targets among DEGs were detected, and sex-specific interactome network maps were generated, indicating the regulatory TFs based on their effects on DEGs and furthermore, on the processes leading to the formation of different-sex flowers. Among the most overrepresented TF families in the sex comparisons were the NAC, bHLH, MYB, and bZIP families. An interaction network analysis indicated the most abundant families among DEGs’ regulatory TFs were MYB, AP2/ERF, NAC, and bZIP, and those with the most significant impact on developmental processes were identified, namely the AP/ERF family, followed by DOF, MYB, MADS, and others. Thus, the networks’ central nodes and key regulators were identified with respect to male, female, and hermaphrodite forms. Here, we proposed the first model of the regulatory network of TFs that influences the metabolism of sex development in cucumber. These findings may help us to understand the molecular genetics and functional mechanisms underlying sex determination processes. Full article
(This article belongs to the Special Issue Manipulation of Metabolic Pathways by Transcription Factors)
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17 pages, 2388 KiB  
Article
Bone Metabolite Profile Differs between Normal and Femur Head Necrosis (FHN/BCO)-Affected Broilers: Implications for Dysregulated Metabolic Cascades in FHN Pathophysiology
by Alison Ramser, Rachel Hawken, Elizabeth Greene, Ron Okimoto, Brenda Flack, Courtney J. Christopher, Shawn R. Campagna and Sami Dridi
Metabolites 2023, 13(5), 662; https://doi.org/10.3390/metabo13050662 - 16 May 2023
Viewed by 1117
Abstract
Femur head necrosis (FHN), also known as bacterial chondronecrosis with osteomyelitis (BCO), has remained an animal welfare and production concern for modern broilers regardless of efforts to select against it in primary breeder flocks. Characterized by the bacterial infection of weak bone, FHN [...] Read more.
Femur head necrosis (FHN), also known as bacterial chondronecrosis with osteomyelitis (BCO), has remained an animal welfare and production concern for modern broilers regardless of efforts to select against it in primary breeder flocks. Characterized by the bacterial infection of weak bone, FHN has been found in birds without clinical lameness and remains only detectable via necropsy. This presents an opportunity to utilize untargeted metabolomics to elucidate potential non-invasive biomarkers and key causative pathways involved in FHN pathology. The current study used ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC–HRMS) and identified a total of 152 metabolites. Mean intensity differences at p < 0.05 were found in 44 metabolites, with 3 significantly down-regulated and 41 up-regulated in FHN-affected bone. Multivariate analysis and a partial least squares discriminant analysis (PLS-DA) scores plot showed the distinct clustering of metabolite profiles from FHN-affected vs. normal bone. Biologically related molecular networks were predicted using an ingenuity pathway analysis (IPA) knowledge base. Using a fold-change cut off of −1.5 and 1.5, top canonical pathways, networks, diseases, molecular functions, and upstream regulators were generated using the 44 differentially abundant metabolites. The results showed the metabolites NAD+, NADP+, and NADH to be downregulated, while 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) and histamine were significantly increased in FHN. Ascorbate recycling and purine nucleotides degradation were the top canonical pathways, indicating the potential dysregulation of redox homeostasis and osteogenesis. Lipid metabolism and cellular growth and proliferation were some of the top molecular functions predicted based on the metabolite profile in FHN-affected bone. Network analysis showed significant overlap across metabolites and predicted upstream and downstream complexes, including AMP-activated protein kinase (AMPK), insulin, collagen type IV, mitochondrial complex, c-Jun N-terminal kinase (Jnk), extracellular signal-regulated kinase (ERK), and 3β-hydroxysteroid dehydrogenase (3β HSD). The qPCR analysis of relevant factors showed a significant decrease in AMPKα2 mRNA expression in FHN-affected bone, supporting the predicted downregulation found in the IPA network analysis. Taken as a whole, these results demonstrate a shift in energy production, bone homeostasis, and bone cell differentiation that is distinct in FHN-affected bone, with implications for how metabolites drive the pathology of FHN. Full article
(This article belongs to the Special Issue Manipulation of Metabolic Pathways by Transcription Factors)
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15 pages, 1970 KiB  
Article
Identification of the Transcription Factor ATF3 as a Direct and Indirect Regulator of the LDLR
by Sabine Bauer, Jana Eigenmann, Yuqi Zhao, Julia Fleig, Johann S. Hawe, Calvin Pan, Dario Bongiovanni, Simon Wengert, Angela Ma, Aldons J. Lusis, Jason C. Kovacic, Johan L. M. Björkegren, Lars Maegdefessel, Heribert Schunkert and Moritz von Scheidt
Metabolites 2022, 12(9), 840; https://doi.org/10.3390/metabo12090840 - 06 Sep 2022
Cited by 3 | Viewed by 2436
Abstract
Coronary artery disease (CAD) is a complex, multifactorial disease caused, in particular, by inflammation and cholesterol metabolism. At the molecular level, the role of tissue-specific signaling pathways leading to CAD is still largely unexplored. This study relied on two main resources: (1) genes [...] Read more.
Coronary artery disease (CAD) is a complex, multifactorial disease caused, in particular, by inflammation and cholesterol metabolism. At the molecular level, the role of tissue-specific signaling pathways leading to CAD is still largely unexplored. This study relied on two main resources: (1) genes with impact on atherosclerosis/CAD, and (2) liver-specific transcriptome analyses from human and mouse studies. The transcription factor activating transcription factor 3 (ATF3) was identified as a key regulator of a liver network relevant to atherosclerosis and linked to inflammation and cholesterol metabolism. ATF3 was predicted to be a direct and indirect (via MAF BZIP Transcription Factor F (MAFF)) regulator of low-density lipoprotein receptor (LDLR). Chromatin immunoprecipitation DNA sequencing (ChIP-seq) data from human liver cells revealed an ATF3 binding motif in the promoter regions of MAFF and LDLR. siRNA knockdown of ATF3 in human Hep3B liver cells significantly upregulated LDLR expression (p < 0.01). Inflammation induced by lipopolysaccharide (LPS) stimulation resulted in significant upregulation of ATF3 (p < 0.01) and subsequent downregulation of LDLR (p < 0.001). Liver-specific expression data from human CAD patients undergoing coronary artery bypass grafting (CABG) surgery (STARNET) and mouse models (HMDP) confirmed the regulatory role of ATF3 in the homeostasis of cholesterol metabolism. This study suggests that ATF3 might be a promising treatment candidate for lowering LDL cholesterol and reducing cardiovascular risk. Full article
(This article belongs to the Special Issue Manipulation of Metabolic Pathways by Transcription Factors)
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Review

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22 pages, 821 KiB  
Review
Participation of Krüppel-like Factors in Atherogenesis
by Stanislav Kotlyarov and Anna Kotlyarova
Metabolites 2023, 13(3), 448; https://doi.org/10.3390/metabo13030448 - 19 Mar 2023
Cited by 5 | Viewed by 1743
Abstract
Atherosclerosis is an important problem in modern medicine, the keys to understanding many aspects of which are still not available to clinicians. Atherosclerosis develops as a result of a complex chain of events in which many cells of the vascular wall and peripheral [...] Read more.
Atherosclerosis is an important problem in modern medicine, the keys to understanding many aspects of which are still not available to clinicians. Atherosclerosis develops as a result of a complex chain of events in which many cells of the vascular wall and peripheral blood flow are involved. Endothelial cells, which line the vascular wall in a monolayer, play an important role in vascular biology. A growing body of evidence strengthens the understanding of the multifaceted functions of endothelial cells, which not only organize the barrier between blood flow and tissues but also act as regulators of hemodynamics and play an important role in regulating the function of other cells in the vascular wall. Krüppel-like factors (KLFs) perform several biological functions in various cells of the vascular wall. The large family of KLFs in humans includes 18 members, among which KLF2 and KLF4 are at the crossroads between endothelial cell mechanobiology and immunometabolism, which play important roles in both the normal vascular wall and atherosclerosis. Full article
(This article belongs to the Special Issue Manipulation of Metabolic Pathways by Transcription Factors)
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