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; 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：脂质在肥胖介导的败血症中的作用 抽象的 败血症是目前没有特定疗法的重要临床问题。临床研究 表明肥胖与败血症的生存率提高相关。但是，肥胖是一种风险 多种病理的因素，不建议将其作为预防败血症的一种选择。这是， 因此，了解导致肥胖介导的败血症保护的潜在机制 作为发展新型治疗方法的一步。在这项研究中，我们将利用现有的临床 败血症患者得出的数据和生物测量，以探索代谢适应与 肥胖介导的败血症保护。在特定目标1中，我们将评估肥胖状态之间的关联 使用现有的临床数据和来自Ardsnet-Sails的血浆样品，败血症期间血浆脂质水平和血浆脂质水平 临床试验。在特定目标2中，我们将确定血浆脂质水平是否首先影响败血症的结果 将血浆脂质水平与重大败血症相关联，例如死亡率，住院时间长度，器官 功能障碍和相关的生物/生理变量。此外，我们将调查保护性是否 肥胖在改善败血症存活方面的影响被降低脂质的药物rosuvastatin消除。长期 这项工作的目标是识别与败血症中肥胖介导的保护有关的参数，这可以进一步 机械学研究并导致败血症的潜在治疗干预措施的发展。