Peroxisome proliferator-activated receptors (PPAR) belong to the nuclear receptor superfamily of ligand-activated transcription factors. PPAR-α
, first of its three subtypes (α, β, γ) has traditionally been considered an important regulator of lipid metabolism while its role in the regulation of insulin sensitivity has not been recognized until recently. Here we summarize the experimental and clinical studies focusing on the role of PPAR-α in the regulation of insulin sensitivity. In most of the experimental studies the activation of PPAR-α in rodents leads to improvement of insulin sensitivity by multiple mechanisms including improvement of insulin signaling due to a decrease of ectopic lipids in
non-adipose tissues and decrease of circulating fatty acids and triglycerides
. In contrast, the effect of PPAR-α agonist in humans is much less pronounced probably due to a lower expression of PPAR-α relative to rodents and possibly other mechanisms. Further clinical studies using more potent PPAR-α agonists on a larger population need to be performed to
evaluate the possible role of PPAR-α in the regulation of insulin sensitivity in humans.
Free fatty acids (FFAs) are natural ligands of the PPARγ2 receptor. FFA plasma concentration and composition may represent one of the factors accounting for high heterogeneity of conclusions concerning the effect of the Pro12Ala on BMI, insulin sensitivity or diabetes type 2 (DM2) susceptibility. Our objective was to investigate the relation and possible interactions between the Pro12Ala polymorphism and FFA status, metabolic markers, and body composition in 324 lean nondiabetic subjects (M/F: 99/225; age 32±11 years; BMI 23.9±4.0 kg/m2) with and without family history of DM2. Family history of DM2 was associated with lower % PUFA and slightly higher % MUFA. The presence of Pro12Ala polymorphism was not associated with fasting plasma FFA concentration or composition, anthropometric or metabolic markers of glucose and lipid metabolism in tested population. However, the interaction of carriership status with FFA levels influenced the basal glucose levels, insulin sensitivity and disposition indices, triglycerides, HDL-cholesterol and leptin levels, especially in women. The metabolic effects of 12Ala carriership were influenced by FFA levels – the beneficial role of 12Ala was seen only in the presence of low concentration of plasma FFA. Surprisingly, a high PUFA/SFA ratio was associated with lower insulin sensitivity, the protective effect of 12Ala allele was apparent in subjects with family history of DM2. On the basis of our findings and published data we recommend the genotyping of diabetic patients for Pro12Ala polymorphism of the PPARγ2 gene before treatment with thiazolidinediones and education of subjects regarding diet and physical activity, which modulate metabolic outcomes., B. Bendlová, D. Vejražková, J. Včelák, P. Lukášová, D. Burkoňová, M. Kunešová, J. Vrbíková, K. Dvořáková, K. Vondra, M. Vaňková., and Obsahuje bibliografii a bibliografické odkazy