PB0887 - Platelet function in MS-NASH mice: a newly developed obesity model

Background: Obesity is a multifactorial disease with many co-morbidities leading to multi-organ dysfunction. It is also associated with recurrent atherothrombotic events and inadequate responses to antiplatelet therapy. Current studies point towards the dysregulation of platelet signaling in both receptor and second messenger pathways as being key drivers for increased risk of atherosclerosis and cardiovascular disease in obesity. However, data from these studies are conflicting and warrant more experimentation to understand platelet function in metabolic disease. Recently, a new mouse model, MS-NASH, was developed to study obesity. This inbred, polygenic, mouse model is clinically translatable given its ability to respond to anti-diabetic drugs, its intact leptin pathway, and its mimicry of the multifaceted aspects of the human metabolic syndrome, disease pathophysiology, and associated comorbidities.

Aims: This study aims to evaluate platelet phenotypes in the MS-NASH, obese mouse model.

Methods: Twelve-week-old MS-NASH mice (Strain #030888, Jackson Laboratory) and C57BL/6J mice were fed a Purina 5008 chow. To validate the model, food intake and weight were recorded. EchoMRI was used to determine fat, lean, free water, and total water mass. Tail-bleeding assays were used to characterize the hemostasis phenotype.

Results: MS-NASH mice had higher overall weight, fat percentage, and total water mass, corresponding with an increased food intake. Lean and free water mass were unaltered. Bleeding times were increased in the MS-NASH mice compared to the C57BL/6J mice (p < 0.0001). Interestingly, bleeding time and body weight positively correlated in the MS-NASH mice.

Conclusion(s): Based on this preliminary study, we validated MS-NASH mice as a model for obesity. Furthermore, we demonstrated that the MS-NASH mice have increased bleeding times which are positively correlated with their body mass, suggesting dysfunctional hemostasis in these obese mice.

This work is supported by the NIH/NHLBI (HL150818), VA, and the CCTS TL1 fellowship (TR 1997-5 A1).