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
PPAR gamma. 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.