Western Diet Modifies Platelet Activation Profiles in Male Mice

Authors: CORKEN, ADAM - University Arkansas For Medical Sciences (UAMS); WAHL, ELIZABETH - Arkansas Children'S Nutrition Research Center (ACNC); SIKES, JAMES - Arkansas Children'S Nutrition Research Center (ACNC); THAKALI, KESHARI - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/17/2024
Publication Date: 7/23/2024
Citation: Corken, A., Wahl, E.C., Sikes, J.D., Thakali, K.M. 2024. Western Diet Modifies Platelet Activation Profiles in Male Mice. International Journal of Molecular Sciences. 25(15):8019. https://doi.org/10.3390/ijms25158019.
DOI: https://doi.org/10.3390/ijms25158019

Interpretive Summary: When people become overweight due to poor nutrition there is a high likelihood that they will develop cardiovascular disease (CVD). Having CVD increases one’s chances of experiencing a heart attack or stroke which occurs when small cells in the bloodstream known as platelets form clots that block blood flow to the heart or brain. Normally platelets only form clots to plug holes in blood vessels when a person is injured to limit blood loss but we’re uncertain of how poor nutrition might encourage platelets to form clots that block blood flow to important organs instead. With that in mind, we began feeding laboratory mice a poor diet that was high in fat, sugar and salt, and then checked for changes in how their platelets work. We saw that this poor diet caused platelets to increase the use of specific tools needed to form clots while decreasing the use of others. We found that this change persisted over the many months that we observed the mice. This is an important discovery to learn that poor nutrition does change the behavior of the platelet. Our findings bring about many more questions about how poor nutrition specifically influences the internal machinery of the platelet to cause the preference of certain clotting tools over others. If we continue to work our way through this initial discovery to learn all the important parts and mechanisms a poor diet uses to change platelets then perhaps we would be able to develop ways to unlink poor nutrition from heart attacks and strokes. And so, our finding is in an important first step in the research journey that could be beneficial to the millions of individuals who suffer from poor nutrition and CVD.

Technical Abstract: The correlation between obesity and cardiovascular disease has long been understood, yet scant investigations endeavored to determine the impact of an obesogenic diet on platelet activation or function. As platelets drive clot formation, the terminus of cardiovascular events, we aimed to elucidate the longitudinal effect of an obesogenic diet on platelet phenotype by assessing markers of platelet activation using flow cytometry. Male, weanling mice were fed either a Western diet (30% kcal sucrose, 40% kcal fat, 8.0% sodium) or Control diet (7% kcal sucrose, 10% kcal fat, 0.24% sodium). At 12, 16 and 20 weeks on diets, platelets were collected and stained to visualize glyco-protein Ib' (GPIb'', P-selectin and the conformationally active state of 'IIb'3 (a platelet specific integrin) after collagen stimulation. At all time points a Western diet reduced GPIb' and 'IIb'3 expression in platelets broadly while P-selectin levels were unaffected. However, P-selectin was diminished by a Western diet in the GPIb'- subpopulation. Thus, a Western diet persistently primed platelets towards a blunted activation response as indicated by reduced active 'IIb'3 and P-selectin surface expression. This study provides a first look at the influence of diet on platelet activation and revealed that platelet activation is susceptible to dietary intervention.