Does Pro¹²Ala Polymorphism Enhance the Physiological Role of PPARγ2?

Abstract

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 (PPARγ2) plays an important role in the lipid metabolism. Since PPARγ2 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 PPARγ2 (OR = 0.702 with 95% CI: 0.622; 0.791, P < 0.01). Conversely the same polymorphism Pro12Ala of PPARγ2 seems to favor obesity since 1.196 more chance than nonobese was found (OR = 1.196 with 95% CI: 1.009; 1.417, P < 0.004). Our results suggest that Pro12Ala polymorphism enhances both adipogenic and antidiabetogenic physiological role of PPARγ. Does Pro12Ala polymorphism represent an evolutionary step towards the stabilization of the molecular function of PPARγ transcription factor signaling pathway?

Peroxisome proliferator-activated receptor-γ polymorphism (rs1801282) is associated with obesity in Egyptian patients with coronary artery disease and type 2 diabetes mellitus

“…The idea of this work was built on determining a genetic marker for prediction or early detection of CAD in diabetic patients, and we found that, PPAR-γ Pro12Ala polymorphism (rs1801282) was more frequent in diabetic patients with CAD complications than those with diabetes only, thus PPAR-γ Pro12Ala polymorphism increased the risk of CAD among diabetic patients. Our findings are in agreement with a huge study includes approximately 11500 individuals, from which 3870 are obese and 7625 are diabetic [32]. This study correlated the PPAR-γ Pro12Ala polymorphism with obesity and other factors of metabolic syndrome in diabetic patients with CVD.…”

Association of the Pro12Ala, C161-T polymorphisms in the PPARγ2 gene with obesity in Han nationality of Yunnan Plateau in Southwest China

“…The PPARγ2 Pro12Ala polymorphism has been widely implicated in affecting the risk of obesity (25),although genetic evidence of its effect on obesity is inconsistent. In this study, single locus analysis did not show a signi cant main effect of PPARγ2 Prol2Ala (in genotypic test, or odds ratio analysis) on the risk of obesity in the whole sample population.…”

Enhanced 3T3-L1 Differentiation into Adipocytes by Pioglitazone Pharmacological Activation of Peroxisome Proliferator Activated Receptor-Gamma (PPAR-γ)

“…Pioglitazone is an insulin-sensitizing drug from the thiazolidinediones family [ 1 ] that strongly activates the transcription factor peroxisome proliferator-activated receptor gamma (PPAR-γ) [ 2 , 3 , 4 , 5 , 6 , 7 ]. Due to its biological effects, pioglitazone is widely used as a type 2 diabetes (T2D) treatment, and several studies have shown that PPAR-γ activation can be directly correlated with insulin sensibilization and the regulation of lipidic metabolism ( Figure 1 ) [ 2 , 4 , 6 ].…”

“…The activation of PPAR-γ by pioglitazone seems to play a role in adipocyte differentiation [ 13 ], apoptosis, and hypertrophy, by increasing adiponectin expression [ 14 ], as well as the control of inflammatory cascades via the reduction of tumor necrosis factor α (TNF-α) [ 2 , 3 , 7 ] and interleukin 6 (IL-6) expression [ 6 , 7 ]. Nevertheless, the biological mechanisms of PPAR-γ activation by pioglitazone remains unestablished.…”