Abstract Number: PB1019
Meeting: ISTH 2021 Congress
Background: Obesity, a nationwide health issue, has related medical costs ranging between $147-210 billion per year in United States and is associated with a 3.5-fold increased risk of developing NAFLD. In obesity, platelets work in a pleotropic manner with vascular and immune cells to amplify the chronic inflammatory process. The emerging role of activated platelets during obesity induced inflammation introduces the novel concept of platelet targeted therapeutic interventions.
TREM-Like Transcript-1 (TLT-1) is a platelet specific receptor found in the α-granules of platelets and released to the surface upon platelet activation. TLT-1 facilitates platelet aggregation and regulates immune mediated inflammatory bleeding. When placed on a western diet, treml1-/- mice are more prone to weight gain and hyperlipidemia.
Aims: Evaluate the effects of western diet on obesity and NAFLD in the treml1-/- mouse model.
Methods: TLT-1 (treml1-/-) and Apolipoprotein E (apoe-/-) double null (AT-DKO;n=11) mice and control apoe+/-/treml1+/- littermate controls (AT-Hets;n=20) were fed western diet for 20 weeks and plasma samples were evaluated for obesity related parameters.
Results: Overall AT-DKO mice gained more weight compared to AT-Hets (12.94±8.34 vs 8.51±1.573 grams p=0.02). Plasma analysis demonstrates that the AT-DKO have higher levels of TNF-α (0.54±0.599 vs 0.118±0.192 pg/ml p=0.03), and IL10 (2.49±1.422 vs 1.51±2.23 pg/ml p=0.004) compared to littermate controls. Histological analysis of livers illustrates increased lipid vacuoles and inflammatory foci in the AT-DKO mice as compared to controls, while preliminary data is not significant for these differences, liver damage in the AT-DKO was significantly greater as demonstrated by increased AST levels (178.57±89.48 vs 102±68.10 U/L p=0.02).
Conclusions: Mutant AT-DKO mice are more prone to obesity and NAFLD compared to littermate controls, suggesting that TLT-1, a platelet gene, plays a surprising role in metabolism and may be an intervention target. The current state of this project will be reported here.
To cite this abstract in AMA style:Branfield S, Nieves Lopez B, Poynter M, Washington AV. Charactering the Role of TLT-1 in Inflammatory Pathogenesis of Obesity and Nonalcoholic Fatty Liver Disease (NAFLD) [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/charactering-the-role-of-tlt-1-in-inflammatory-pathogenesis-of-obesity-and-nonalcoholic-fatty-liver-disease-nafld/. Accessed May 16, 2022.
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