STAT1 and STAT6 Act as Antagonistic Regulators of PPARγ in Diabetic Patients with and without Cardiovascular Diseases

Background: The processes that mediate an inflammatory environment and increase atherosclerosis in diabetes are not well understood. Peroxisome proliferator-activated receptors (PPARs) are a subgroup of the nuclear hormone receptor superfamily of ligand-activated transcription factors which play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) and atherosclerosis. PPAR gamma promotes changes in lipid metabolism, especially in fatty acid (FA) trafficking, and the activity of PPAR gamma could be modulated by diabetes phenotype patients. Fatty acid translocase CD36 is one of the advanced PPAR gamma targets to arbitrate this action. In the current study, we investigated the potential role of signal transducer and activator of transcription STAT1 and STAT6 signaling linked to PPAR gamma and its implication in the modulation of lipid metabolism. Methods: Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to quantify target genes in Peripheral Blood Mononuclear Cells (PBMCs) isolated from two diabetic groups: diabetic patients with cardiovascular diseases (D.CVD) and without cardiovascular diseases (D). Results: We demonstrated that PPAR gamma and CD36 mRNA expressions were downregulated along D.CVD compared to D (p = 0.002; p = 0.04; respectively). Decreased CD36 was accompanied by elevated levels of plasma triglyceride (TG) concentrations, 0.83 +/- 0.29 vs. 2.46 +/- 0.22), respectively. Furthermore, STAT1 was significantly more expressed in D.CVD (p = 0.01). On the other hand, we demonstrated that STAT6 induces a significant level of PPAR gamma mRNA expression in D patients (p = 0.01). Conclusions: Our results suggest that the expression and activity of PPAR gamma mediates CD36 in PBMCs and varies with respect to STAT6 and STAT1 trafficking in diabetic patients with and without cardiovascular diseases.