The Role of PPARs in Disease - Volume III

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

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

• The Role of PPARs in Disease in Cells (11 articles)
• The Role of PPARs in Disease II in Cells (20 articles)

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.