The Role of Lipids in Obesity-mediated Protection in Sepsis

标题：脂类在脓毒症肥胖调节保护中的作用 摘要 脓毒症是一个重要的临床问题，目前还没有特效的治疗方法。临床研究 表明肥胖与脓毒症患者存活率的提高有矛盾的联系；然而，由于肥胖是一种风险 对于多种病理因素，不推荐将其作为预防脓毒症的选择。它是, 因此，了解导致脓毒症中肥胖介导保护的潜在机制很重要。 作为开发新的治疗方法的一步。在这项研究中，我们将利用现有的临床 来自脓毒症患者的数据和生物样本，以探索代谢适应和 脓毒症中肥胖介导的保护作用。在具体目标1中，我们将评估肥胖状况与 利用现有的临床数据和ARDSNet-SAILS的血浆样本研究脓毒症期间的血脂水平 临床试验。在特定的目标2中，我们将首先确定血脂水平是否影响脓毒症的预后 血脂水平与主要败血症结局的相关性，如死亡率、住院时间、器官 功能障碍，以及相关的生物/生理变量。此外，我们将调查是否有保护措施 肥胖在改善脓毒症存活率方面的作用被降脂药物瑞舒伐他汀消除。长期的 这项工作的目标是确定与脓毒症中肥胖介导的保护相关的参数，这可以进一步 对脓毒症进行了机械研究，并导致了可能的治疗干预措施的开发。

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.