The
nuclear receptors PPAR (
Peroxisome Proliferator-Activated Receptors) are
transcription factors which form with the
retinoid receptor RXR, a
PPAR/RXR heterodimer, the functional
transcription factor within cells.
PPAR receptors are activated by their
ligands, either naturals or synthetics, and modulate target gene transcription. There are three
PPAR subtypes (
PPARalpha,
PPARbeta/delta et
PPARgamma) coded by different genes, and two
isoforms of
PPARgamma proteins have been detected in humans (PPARgamma1 and
PPARgamma2).
PPAR are mainly modulators of lipid metabolism, but each receptor subtype is pharmacologically distinct, and development of synthetic
PPAR agonists has shown their role in cellular (mainly adipocyte) differentiation and in
glucose homeostasis. This review summarise the main data, currently available, on expression,
biological functions, natural and synthetic (activators)
ligands for the
PPAR receptor subtypes.
PPAR receptors key-role in
lipid and
glucose métabolisms, has lead to a large clinical use of pharmacological agents acting as
PPAR ligands:
fibrates,
PPARalpha agonists as hypolipidaemic treatment,
thiazolidinediones (
glitazones),
PPARalpha agonists as
antidiabetics. Lipid metabolism is impaired in
insulin resistant skeletal muscles,
fatty acids role in the pathophysiology of
insulin resistance generates several hypothesis we briefly describe. Finally, we present and discuss experimental data, suggesting the activation of
PPARbeta/delta in skeletal muscle to be a potential new approach in the treatment of
insulin resistance and
metabolic syndrome.