The worldwide prevalence of obesity has increased at alarming rates over
the last four decades. Overweight and obesity featuring the excess of white adipose
tissue are cardiovascular risk conditions consistently associated with the development
of complex metabolic disorders, including insulin resistance, type 2 diabetes mellitus (
T2DM) and coronary heart diseases. Many natural and synthetic agonists of
peroxisome proliferator-activated receptors (PPARs; nuclear receptors) are used in the
treatment of glucose and lipid disorders. PPARs perform different activities, mainly via
endogenous ligands produced in the metabolic pathways of fatty acids; and therefore,
they are called lipid sensors. PPAR agonists have different properties and specificities
for individual PPAR receptor, different absorption/distribution profiles, and distinct
gene expression profiles, which ultimately lead to different clinical outcomes. The
isoform PPARγ is expressed in white and brown adipose tissue, large intestine and
spleen. However, its expression is highest in adipocytes and it plays a key role in the
adipogenesis regulation, energy balance and lipid biosynthesis. PPARγ has been the
focus of intense research once its ligands have been described to treat T2DM. Some of
them are currently prescribed as anti-diabetic drugs, such as thiazolidinedione. PPARγ
activation modulates not only insulin sensitization, but also lipid metabolism, vascular
tone and inflammation, all processes involved in atherogenesis. Considering the impact
of this subject in the public health and the necessity of new approaches for the
development of new drugs to treat metabolic diseases and to improve the quality of life,
this chapter has the aim of revising important points concerning the involvement of the
nuclear receptors in obesity, diabetes and discuss the real possibility of this target to
become an effective and safe pharmacological therapy.
Keywords: Adipogenesis, Agonist, Diabetes, Glitazones, Hyperglycaemia,
Metabolic syndrome, Nuclear receptors, Obesity, PPARγ, Peroxisome.
