Obesity and type 2 diabetes mellitus (T2D) are two major public health problems that have motivated the scientific community to investigate the high contribution of genetic factors to these disorders. The peroxisome proliferator activated by gamma 2 (PPAR 2) plays an important role in the lipid metabolism. Since PPAR 2 is expressed mainly in adipose tissue, a moderate reduction of its activity influences the sensitivity to insulin, diabetes, and other metabolic parameters. The present study aims to contribute to the elucidation of the impact of the Pro12Ala polymorphism associated with T2D and obesity through a meta-analysis study of the literature that included approximately 11500 individuals, from which 3870 were obese and 7625 were diabetic. Statistical evidence supports protective effect in T2D of polymorphism Pro12Ala of PPAR 2 (OR？=？0.702 with 95% CI: 0.622; 0.791, ). Conversely the same polymorphism Pro12Ala of PPAR 2 seems to favor obesity since 1.196 more chance than nonobese was found (OR？=？1.196 with 95% CI: 1.009; 1.417, ). Our results suggest that Pro12Ala polymorphism enhances both adipogenic and antidiabetogenic physiological role of PPAR . Does Pro12Ala polymorphism represent an evolutionary step towards the stabilization of the molecular function of PPAR transcription factor signaling pathway? 1. Introduction Peroxisome proliferator-activated receptors (PPARs) are transcription factors from nuclear receptor’s protein family that regulate target genes’ expression by connecting to response elements of peroxisomes proliferators (PPERs) in regulating sites of each gene. The signal transduction mechanism of these receptors involves retinol X receptor (RXR) and PPARs form heterodimers that regulate the transcription of several genes (Figure 1) [1–3]. Figure 1: PPAR transduction pathway. PPAR has several extracellular and intracellular ligands that include dietary and bioactive lipids. Given its antidiabetogenic role, some PPAR ligands include antidiabetic drugs such as thiazolidinediones. PPAR is also modulated by several growth factor transduction pathways such as Jnk/Erk/MKP. It is also known that cyclin-dependent kinase 5 (Cdk5) bond to p25 (a product of the cleavage of p35 in obesity environment) inhibits PPAR pathway by its phosphorylation. As a transcriptional factor, PPAR binds to RXR (retinol X receptor) in order to transcribe several genes related to adipocyte differentiation and lipid storage in adipose tissue and increase insulin sensitivity in peripheral tissues by indirect increase of AMP kinase activity as well as several other
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