IMR Press / FBL / Volume 19 / Issue 6 / DOI: 10.2741/4257

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Review
Cross-talk between heme oxygenase and peroxisome proliferator-activated receptors in the regulation of physiological functions
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1 Department of Physiology, University of Saskatchewan College of Medicine, 107 Wiggins Road, Saskatoon, SK, Canada
Academic Editor:Joseph Fomusi Ndisang
Front. Biosci. (Landmark Ed) 2014, 19(6), 916–935; https://doi.org/10.2741/4257
Published: 1 June 2014
Abstract

Peroxisome-proliferator-activated-receptors (PPARs) are transcription factors belonging to the superfamily of nuclear receptors. The isoforms of PPAR include PPAR alpha, PPAR gamma and PPAR delta (also known as PPAR beta). Generally, PPARs potentiate insulin sensitivity, improve glucose/lipid metabolism, suppress inflammation/oxidative stress, attenuate excessive immune responses, regulate cell-growth and differentiation. Interestingly, agonists of PPAR gamma and PPAR alpha have been shown to upregulate the heme-oxygenase (HO)- system. Conversely, the HO-system also enhances PPAR alpha, and potentiates the expression and activity of PPARg. Moreover, the HO-system and related products including bilirubin, biliverdin, carbon monoxide and ferritin have been shown to increase insulin sensitivity, improve glucose/lipid metabolism, suppress inflammation/oxidative stress, abate immune response, and modulate cell-growth/differentiation. Therefore, an intimate, reciprocal, stimulatory and synergistic relationship between PPAR-signaling and the HO-system can be envisaged in the regulation of physiological functions. Thus, both the HO-system and PPARs-signaling participate in fine-tuning similar physiological functions, so novel pharmacological agents capable of optimizing this interaction should be sought. The coordinated regulation of PPAR-signaling and the HO-system may constitute the basis for future drug design.

Keywords
Heme oxygenase
Diabetes
Peroxisome proliferator-activated receptor
Oxidative stress
Inflammation
Review
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