The Role of PPARs in Disease - Volume III

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 31 July 2024 | Viewed by 743

Special Issue Editors


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Guest Editor
Institute of Biology Valrose, University of Nice Sophia Antipolis, 06107 Nice, France
Interests: PPARs; cancer; development; angiogenesis; transcriptional regulation; tumor angiogenesis; mechanisms of tumor progression; cancer treatment
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Special Issue Information

Dear Colleagues,

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors. They function as ligand-activated transcription factors. They exist in three isoforms, i.e., PPARα, PPARβ/δ, and PPARγ. For all PPARs, lipids are endogenous ligands, linking them directly to metabolism. PPARs form heterodimers with retinoic X receptors and, upon ligand binding, modulate the gene expression of downstream target genes, depending on the presence of co-repressors or co-activators. This results in a complex, cell-type-specific regulation of proliferation, differentiation, and cell survival. Specific synthetic agonists for all PPARs are available. PPARα and PPARγ agonists are already in clinical use for the treatment of hyperlipidemia and type 2 diabetes, respectively. More recently, PPARβ/δ activation came into focus as an interesting novel approach for the treatment of metabolic syndrome and associated cardiovascular diseases.

In summary, PPARs are linked to metabolic disorders and are interesting pharmaceutical targets. PPARs play important roles in a variety of disorders, e.g., cardiovascular, hepatic, neurological, psychiatric, and immunological diseases and cancer. We guest-edited the first Special Issue on “The Role of PPARs in Disease” of Cells in 2019–2020. Despite the global health crisis, 11 papers were published in this Special Issue, which have received until now more than 60,000 views and more than 450 citations. In 2021–2022, we guest-edited the second Special Issue on the topic “The Role of PPARs in Disease II”. This Special Issue attracted even higher attention. Overall, 20 papers were finally published in this Special Issue, which have already received nearly 52,000 views and 130 citations.

We hope that this new Special Issue of Cells, with the continuous efforts of the scientific community, will be equally or even more successful. This Special Issue will bring together the most recent and exciting advances in understanding the various aspects of the action of PPARs, from basic science to applied therapeutic approaches.

Sincerely,

Dr. Kay-Dietrich Wagner
Dr. Nicole Wagner
Guest Editors

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. Cells is an international peer-reviewed open access semimonthly 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

  • PPAR
  • immune function
  • liver
  • adipose tissue
  • cardiovascular system
  • muscle
  • neurological and psychiatric diseases
  • cancer
  • transcriptional regulation
  • ligands
  • agonists/antagonists

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Published Papers (1 paper)

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Research

12 pages, 2038 KiB  
Article
CBFA2T3 Is PPARA Sensitive and Attenuates Fasting-Induced Lipid Accumulation in Mouse Liver
by Donghwan Kim, Sang Keun Ha and Frank J. Gonzalez
Cells 2024, 13(10), 831; https://doi.org/10.3390/cells13100831 - 13 May 2024
Viewed by 380
Abstract
Peroxisome proliferator-activated receptor alpha (PPARA) is a ligand-activated transcription factor that is a key mediator of lipid metabolism and metabolic stress in the liver. Accumulating evidence shows that PPARA regulates the expression of various protein coding and non-coding genes that modulate metabolic stress [...] Read more.
Peroxisome proliferator-activated receptor alpha (PPARA) is a ligand-activated transcription factor that is a key mediator of lipid metabolism and metabolic stress in the liver. Accumulating evidence shows that PPARA regulates the expression of various protein coding and non-coding genes that modulate metabolic stress in the liver. CBFA2/RUNX1 partner transcriptional co-repressor 3 (CBFA2T3) is a DNA-binding transcription factor that belongs to the myeloid translocation gene family. Many studies have shown that CBFA2T3 is associated with acute myeloid leukemia. Especially, CBFA2T3–GLIS2 fusion is a chimeric oncogene associated with a poor survival rate in pediatric acute megakaryocytic leukemia. A previous study identified that PPARA activation promoted Cbfa2t3 induction in liver and that Cbfa2t3 may have a modulatory role in metabolic stress. However, the effect of CBFA2T3 gene expression on metabolic stress is not understood. In this study, the PPARA ligand WY14643 activated Cbfa2t3 expression in mouse liver. Glucose tolerance test and insulin tolerance test data showed that insulin resistance is increased in Cbfa2t3−/− mice compared to Cbfa2t3+/+ mice. Hepatic CBFA2T3 modulates heat shock protein family A member 1b and carbonic anhydrase 5a expression. Histology analysis revealed lipid droplet and lipid accumulation in the liver of fasting Cbfa2t3−/− mice but not Cbfa2t3+/+ mice. The expression of lipid accumulation-related genes, such as Cd36, Cidea, and Fabp1, was increased in the liver of fasting Cbfa2t3−/− mice. Especially, basal expression levels of Cidea mRNA were elevated in the liver of Cbfa2t3−/− mice compared to Cbfa2t3+/+ mice. Much higher induction of Cidea mRNA was seen in the liver of Cbfa2t3−/− mice after WY14643 administration. These results indicate that hepatic CBFA2T3 is a PPARA-sensitive gene that may modulate metabolic stress in mouse liver. Full article
(This article belongs to the Special Issue The Role of PPARs in Disease - Volume III)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: The role of Endothelial dysfunction in MASLD
Authors: Ana P Madariaga T, Varenka J Barbero Becerra
Affiliation: Medica Sur Clinic & Foundation
Abstract: n/a

Title: Tumor Suppressor Par-4 Regulates Adipogenesis via Transcriptional Repression of PPARγ
Authors: Vivek M. Rangnekar
Affiliation: na
Abstract: n/a

Title: Role of 4-thiazolidinone-pyrazoline/indoline hybrids Les-4369 and Les-3467 in BJ and A549 cell lines
Authors: Karolina Kosińska; Bartosz Skóra; Serhii Holota; Yulia Shepeta; Anna Tabęcka-Łonczyńska; Roman Lesyk; Konrad A. Szychowski
Affiliation: Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225 Rzeszow, Poland
Abstract: Cancer is one of the most important problems of modern societies. Recently, studies have reported the anticancer properties of rosiglitazone related to its ability to bind peroxisome proliferator receptor γ (PPARγ), which has various effects on cancer and can inhibit cell proliferation. In this study, we investigated the effect of new 4-thiazolidinone (4-TZD) hybrids Les-4369 and Les-3467 and their effect on reactive oxygen species (ROS) production, metabolic activity, lactate dehydrogenase (LDH) release, caspase-3 activity, and gene and protein expression in human foreskin fibroblast (BJ) cells and lung adenocarcinoma (A549) cells. The ROS production and caspase-3 activity were mainly increased in the micromolar concentrations of the studied compounds in both cell lines. Les-3467 and Les-4369 increased the mRNA expression of PPARG, P53 (tumor protein P53), and ATM (ATM serine/threonine kinase) in the BJ cells, while the mRNA expression of these genes (except PPARG) was mainly decreased in the A549 cells treated with both of the tested compounds. Our results indicate a decrease in the protein expression of AhR, PPARγ, and PARP-1 in the BJ cells exposed to 1 µM Les-3467 and Les-4369. In the A549 cells, the protein expression of AhR, PPARγ, and PARP-1 increased in the treatment with 1 µM Les-3467 and Les-4369. We have also shown PPARγ modulatory properties of Les-3467 and Les-4369. However, both compounds prove weak anticancer properties evidenced by their action at high concentrations and non-selective effects against BJ and A549 cells.

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