The Role of Lipids in Obesity-mediated Protection in Sepsis

标题：脂质在败血症中肥胖介导的保护作用

TITLE: The role of lipids in 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 the 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 evaluate the association between obesity status and plasma lipid levels during sepsis using existing clinical data and plasma samples from the ARDSNet-SAILS clinical trial. In Specific Aim 2, we will determine whether plasma lipid levels influence sepsis outcomes by first correlating plasma lipid levels with major sepsis outcomes such as mortality, length of hospital stay, organ dysfunction, and related biological/physiological variables. Additionally, we will investigate whether the protective effect of obesity in improving sepsis survival is abolished with the lipid-lowering drug rosuvastatin. The long-term goal of this work is to identify parameters related to obesity-mediated protection in sepsis, which can be further mechanistically investigated and lead to the development of potential therapeutic interventions for sepsis.