Platelet Activation in High Fat Diet-Fed Mice

Diabetes Mellitus (DM) is prevalent in 25.8 million Americans with an additional 79 million exhibiting prediabetes. Interestingly, the major cause of morbidity and mortality in diabetic patients results from macrovascular and microvascular complications.  DM is characterized by high circulating glucose concentrations as well as increased fatty acids in the blood, leading to altered metabolic utilization of substrates in diabetic patients. Metabolic function is extremely important in platelets due to a high-energy requirement for activation.  In patients with metabolic syndrome (MS) and type II diabetes mellitus (T2DM), high circulating glucose has been correlated to increased platelet activation and vascular complications.  However, the mechanisms underlying these alterations are currently unknown.  Therefore, the present study aims to characterize platelet activation in a mouse model of MS and T2DM. Mice were fed normal chow (NCD) or a high fat diet (HFD) for 17 weeks to induce MS and T2DM.  Platelets were isolated from HFD (n=7) and NCD (n=5) fed mice, then incubated with five agonists (Thrombin, PAR4, PMA, U46619, and ADP), and monitored for P-selectin and αIIbβ₃ activation.  Platelets were examined using flow cytometry gating for platelet activation and mean fluorescence intensity. Platelets from HF-fed mice displayed decreased sensitivity towards ADP.  Together these data indicate mice treated with a high fat diet display agonist specific alterations of platelet activation.