Pharmacological Mechanism of PPARγ Ratio in Diabetes and Obesity
- Pp. 199-225 (27)Jose Roberto Santin, Marina Jagielski Goss and Nara Lins Meira Quintao
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.