The Role of PPARs in Disease - Volume IV

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Cardiovascular System".

Deadline for manuscript submissions: 30 November 2026 | Viewed by 2968

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,

The first identification of peroxisomes was made in electron microscopic studies in 1954. In the 1970s, peroxisome proliferators were defined as substances that induce peroxisome growth. Later, in the 1990s, the receptors for these substances (peroxisome proliferator-activated receptors (PPARs)) were cloned and identified. This is an unusual timeline in terms of drug development strategies, as the ligands were discovered almost 20 years before the receptors.

It is now common knowledge that PPARs belong to the nuclear receptors. They function as ligand-activated transcription factors. There are three isoforms: PPARα, PPARβ/δ and PPARγ. For all PPARs, lipids are endogenous ligands, linking them directly to metabolism. Specific synthetic agonists for all PPARs are available. PPARα and PPARγ agonists are used in clinical practice to treat hyperlipidaemia and type 2 diabetes, respectively. More recently, activation of PPARβ/δ has emerged as a promising novel approach for treating metabolic syndrome and associated cardiovascular diseases. PPARs play important roles in various disorders, including cardiovascular, hepatic, neurological, psychiatric, immunological diseases, and cancer.

We guest-edited the first special issue of Cells, entitled 'The Role of PPARs in Disease', in 2019–2020, followed by the second and third editions in subsequent years. These special issues have published a total of 41 papers on PPAR function, which have obtained over 200,000 views and nearly 1,000 citations to date. These figures demonstrate that Cells has become an important platform for excellent research in the field of PPARs.

We hope that this new special issue of Cells, with the continued support of the scientific community, will be equally or even more successful. This special issue will bring together the most recent and exciting advances in our understanding of the various aspects of PPAR action, from basic science to applied therapeutic approaches.

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

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Keywords

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

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Published Papers (3 papers)

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14 pages, 5826 KB  
Article
Molecular Iodine/PPARγ Interaction in the Invasion and Angiogenesis of Neuroblastoma Xenografts
by Edgar R. Juvera-Avalos, Gustavo Orizaga-Osti, Evangelina Delgado-Gonzalez, Hilda Lomeli, Brenda Anguiano and Carmen Aceves
Cells 2026, 15(13), 1189; https://doi.org/10.3390/cells15131189 - 30 Jun 2026
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Abstract
The study investigates the impact of molecular iodine (I2) supplementation on the viability, invasiveness, and angiogenic potential of high-risk neuroblastoma (NB). In vitro assays were performed using NB cell lines SK-N-AS (non-MYCN-amplified) and SK-N-BE(2) (MYCN-amplified). The role [...] Read more.
The study investigates the impact of molecular iodine (I2) supplementation on the viability, invasiveness, and angiogenic potential of high-risk neuroblastoma (NB). In vitro assays were performed using NB cell lines SK-N-AS (non-MYCN-amplified) and SK-N-BE(2) (MYCN-amplified). The role of peroxisome proliferator-activated receptor gamma (PPARγ) was evaluated using the antagonist GW9662, gene expression (RT-qPCR), and protein levels (Western blot). In vivo, zebrafish xenografts were used to evaluate tumor size, angiogenesis, and caudal cell dissemination. I2 supplementation significantly decreased cell viability in both cell lines, independent of PPARγ activation. In SK-N-BE(2), I2 impaired cell migration, as measured by a wound-healing assay, in apparent independence of PPARγ activation. However, gene expression indicates that I2 acts in complex ways, including direct antioxidant effects and PPARγ-mediated effects. The significant decrease in reactive oxygen species levels (DCFDA staining) and the silencing of the long noncoding RNA myocardial infarction-associated transcript (MIAT) by I2 were directly associated with decreased MYCN and TrkB expression. In contrast, PPARγ activation was accompanied by overexpression of FasN and TrkA and a significant decrease in Aurka, a MYCN-stabilizing protein. In zebrafish, I2-pretreated SK-N-BE(2) xenografts exhibited a clear reduction in angiogenesis (vascular density) and a decrease in invasive capacity. In conclusion, I2 supplementation decreases cell viability and attenuates invasion and angiogenesis in NB cells, highlighting its potential as an adjuvant to conventional therapy for high-risk NB. Full article
(This article belongs to the Special Issue The Role of PPARs in Disease - Volume IV)
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Review

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22 pages, 1985 KB  
Review
PPARα: Linking Cardiac Metabolism to Therapeutic Opportunities in Cardiovascular Diseases
by Maxime Roes, Claude Libert and Jolien Vandewalle
Cells 2026, 15(10), 940; https://doi.org/10.3390/cells15100940 - 20 May 2026
Viewed by 647
Abstract
Peroxisome proliferator-activated receptor alpha (PPARα) is a key transcriptional regulator of lipid metabolism, highly expressed in metabolically active organs such as the heart. In cardiomyocytes, where approximately 70% of energy is derived from fatty acid oxidation, PPARα plays a central role in maintaining [...] Read more.
Peroxisome proliferator-activated receptor alpha (PPARα) is a key transcriptional regulator of lipid metabolism, highly expressed in metabolically active organs such as the heart. In cardiomyocytes, where approximately 70% of energy is derived from fatty acid oxidation, PPARα plays a central role in maintaining metabolic homeostasis. Moreover, the transcription factor is implicated in postnatal maturation of the heart and immune modulation. Dysregulation of PPARα signaling has profound consequences for cardiac energy balance, particularly under stress conditions. Accordingly, its role has been extensively investigated in cardiovascular diseases, including ischemia/reperfusion, diabetic cardiomyopathy and sepsis-induced cardiomyopathy. Upon ischemia/reperfusion and sepsis, cardiac PPARα expression is typically downregulated, contributing to impaired fatty acid breakdown and reduced metabolic flexibility. In contrast, diabetic cardiomyopathy is characterized by sustained PPARα activation, promoting excessive fatty acid oxidation, lipid accumulation and lipotoxicity. These context-dependent effects highlight a complex role of PPARα in cardiac diseases. PPARα has emerged as a promising therapeutic target, as its modulation can alleviate cardiac injury in preclinical models. However, further research is required to validate its efficacy in human disease, improve cardiomyocyte-specific targeting strategies to minimize systemic side effects, and better define optimal timing of intervention, as inappropriate or prolonged modulation may lead to detrimental outcomes. Full article
(This article belongs to the Special Issue The Role of PPARs in Disease - Volume IV)
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17 pages, 750 KB  
Review
Peroxisome Proliferator-Activated Receptor β/δ: A Link Between Metabolism, Inflammation, and Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease
by Xavier Palomer, Jue-Rui Wang, Xiaoman Tang, Siyuan Wu, Ricardo Rodríguez-Calvo, Walter Wahli and Manuel Vázquez-Carrera
Cells 2026, 15(5), 464; https://doi.org/10.3390/cells15050464 - 5 Mar 2026
Cited by 1 | Viewed by 1309
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is considered a hepatic manifestation of insulin resistance and ranges from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH). Hepatocyte ballooning, indicative of hepato-cellular damage, and liver inflammation, with or without fibrosis, are characteristic of MASH. Evidence shows [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is considered a hepatic manifestation of insulin resistance and ranges from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH). Hepatocyte ballooning, indicative of hepato-cellular damage, and liver inflammation, with or without fibrosis, are characteristic of MASH. Evidence shows that peroxisome proliferator-activated receptor β/δ (PPARβ/δ), expressed in the major liver cells (hepatocytes, Kupffer cells, cholangiocytes, and hepatic stellate cells), may help prevent the progression of MASLD by ameliorating insulin resistance, lipotoxicity, inflammation, and fibrosis. In this review, we summarize the molecular mechanisms by which PPARβ/δ attenuates the progression of MASLD and discuss future research perspectives. Full article
(This article belongs to the Special Issue The Role of PPARs in Disease - Volume IV)
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