The Role of Lipids in Obesity-mediated Protection in Sepsis

脂质在肥胖介导的脓毒症保护中的作用

• 批准号: 10729051
• 负责人: Preetha Shridas
• 金额: $ 11.48万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10729051
• 关键词: Abbreviations; Acceleration; Acute; Acute Lung Injury; Acute-Phase Proteins; Adipose tissue; Biological; Biological Specimen Banks; Body mass index; Carbohydrates; Cardiovascular Diseases; Categories; Characteristics; Cholesterol; Citric Acid Cycle; Clinical; Clinical Data; Clinical Research; Clinical Trials; Critical Illness; Data; Development; Energy Supply; Energy-Generating Resources; Fatty Acids; Fever; Functional disorder; Funding Opportunities; Future; Glucose; Goals; Human; Human Biology; Impairment; Inflammation; Ketone Bodies; Length of Stay; Life; Lipids; Lipolysis; Malignant Neoplasms; Measures; Mediating; Medical; Metabolic; Mission; Modeling; National Heart, Lung, and Blood Institute; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; Obese Mice; Obesity; Organ; Outcome; Pathology; Pathway interactions; Patients; Phagocytosis; Pharmaceutical Preparations; Physiological; Placebos; Plasma; Play; Process; Production; Proteins; Recommendation; Reporting; Research; Risk Factors; Role; Sampling; Science; Sepsis; Tachycardia; Therapeutic Intervention; Translational Research; Triglycerides; Up-Regulation; Work; anorexic; data repository; diet-induced obesity; healthy weight; human disease; immune activation; improved; improved outcome; lipid metabolism; mortality; mouse model; novel therapeutic intervention; pre-clinical; protective effect; response; rosuvastatin; septic; septic patients; therapeutic development; translational potential; treatment group

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.

标题：脂质在肥胖介导的脓毒症保护中的作用 摘要 脓毒症是一个重要的临床问题，目前尚无特异性治疗方法。临床研究 表明肥胖与脓毒症生存率的提高矛盾地相关;然而，由于肥胖是一种风险， 由于它是多种病理学的一个重要因素，因此不能推荐它作为预防脓毒症的一种选择。是的， 因此，重要的是要了解导致肥胖介导的脓毒症保护的潜在机制 作为发展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 来自败血症患者的数据和生物标本，以探索代谢适应和 肥胖介导的脓毒症保护作用在具体目标1中，我们将评估肥胖状态与 使用现有的临床数据和来自ARDSNet-SAILS的血浆样本， 临床试验在具体目标2中，我们将首先确定血脂水平是否影响脓毒症结局， 将血浆脂质水平与主要脓毒症结局如死亡率、住院时间、器官功能、 功能障碍和相关的生物学/生理学变量。此外，我们将调查是否保护 肥胖在改善脓毒症存活中的作用被降脂药物瑞舒伐他汀消除。长期 这项工作的目的是确定与肥胖介导的脓毒症保护相关的参数， 机制研究，并导致潜在的治疗干预败血症的发展。