Obesity-mediated protection in sepsis

ABSTRACT Sepsis is a major burden to the healthcare system being the most common cause for admission to the intensive care unit and the most expensive condition treated in US hospitals. It is a complex physiologic condition involving a heterogenous patient population with high morbidity and mortality, and no specific therapies aside from supportive measures. Clinical studies indicate that obesity is paradoxically associated with improved survival in sepsis; however, the mechanisms behind this obesity-mediated protection are not known. Capitalizing on the unique resistance in this patient population may allow for the development of novel therapies to prevent the morbidity and mortality associated with sepsis. The primary goals of my research program are to 1) investigate differences in sepsis pathophysiology in patients stratified by obesity status with a major focus on immune alterations, and 2) define shifts in immune cell function and metabolism in obesity, and determine their roles in conferring protection during sepsis utilizing a validated murine model and patient samples. The gained information will aid in the development strategies to reduce morbidity and mortality in sepsis.