The Role of Lipids in Obesity-mediated Protection in Sepsis

TITLE: Obesity-mediated protection in sepsis ABSTRACT Sepsis is an important clinical problem for which no specific therapies are currently available. Clinical studies indicate that obesity is paradoxically associated with improved survival in sepsis; however, as obesity is a risk factor for a wide variety of pathologies, it cannot be recommended as an option to protect against sepsis. It is therefore important to understand the underlying mechanisms that lead to obesity-mediated protection in sepsis as a step towards development of novel therapeutic approaches. In this study, we will utilize existing clinical data and biospecimens derived from sepsis patients to explore a connection between metabolic adaptation and obesity-mediated protection in sepsis. In Specific Aim 1, we will retrospectively evaluate the association between obesity status and sepsis outcomes using existing clinical data from the ARDSNet-SAILS clinical trial. In Specific Aim 2, we will utilize existing plasma samples from this trial to determine whether obesity-induced alterations in metabolic adaptation associate with sepsis outcomes by measuring multiple biologic parameters associated with lipid metabolism and stratifying these by obesity status. The long-term goal of this work is to identify parameters related to obesity-mediated protection in sepsis which could be further mechanistically investigated and lead to the development of potential therapeutic interventions for sepsis.