Peroxisome Proliferator-Activated Receptors: Experimental Targeting for the Treatment of Inflammatory Bowel Diseases

Juan Decara, Patricia Rivera, Antonio Jesús López-Gambero, Antonia Serrano, Francisco Javier Pavón, Elena Baixeras, Fernando Rodríguez de Fonseca, Juan Suárez
Front. Pharmacol.. 2020-05-27; 11:
DOI: 10.3389/fphar.2020.00730

PubMed

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Decara J(1), Rivera P(2), López-Gambero AJ(1), Serrano A(1), Pavón FJ(1)(3),
Baixeras E(4), Rodríguez de Fonseca F(1), Suárez J(1).

Author information:
(1)UGC Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA),
Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
(2)Departamento de Endocrinología, Fundación Investigación Biomédica del
Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
(3)Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares
(CIBERCV) and UGC del Corazón, Instituto de Investigación Biomédica de Málaga
(IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga,
Málaga, Spain.
(4)Departamento de Bioquímica y Biología Molecular, Facultad de Medicina,
Universidad de Málaga, IBIMA, Málaga, Spain.

The peroxisome proliferator-activated receptors (PPARs) are a group of nuclear
receptor proteins that promote ligand-dependent transcription of target genes
that regulate energy production, lipid metabolism, and inflammation. The PPAR
superfamily comprises three subtypes, PPARα, PPARγ, and PPARβ/δ, with
differential tissue distributions. In addition to their different roles in the
regulation of energy balance and carbohydrate and lipid metabolism, an emerging
function of PPARs includes normal homeostasis of intestinal tissue. PPARα
activation represses NF-κB signaling, which decreases the inflammatory cytokine
production by different cell types, while PPARγ ligands can inhibit activation
of macrophages and the production of inflammatory cytokines, such as tumor
necrosis factor-alpha (TNF-α), interleukin (IL)-6, and Il-1β. In this regard,
the anti-inflammatory responses induced by PPAR activation might restore
physiopathological imbalances associated with inflammatory bowel diseases (IBD).
Thus, PPARs and their ligands have important therapeutic potential. This review
briefly discusses the roles of PPARs in the physiopathology and therapies of the
most important IBDs, ulcerative colitis (UC), and Crohn’s disease (CD), as well
some new experimental compounds with PPAR activity as promising drugs for IBD
treatment.