Effects of Fish Oil on Inflammation and Metabolic Syndrome

鱼油对炎症和代谢综合征的影响

基本信息

批准号：
8274802
负责人：
Philip A Kern
金额：
$ 30.93万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-01 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8274802
关键词：
2,4-thiazolidinedione Adipocytes Adipose tissue Affect Aftercare Agonist Animal Feed Anti-Inflammatory Agents Anti-inflammatory Apoptosis Arachidonic Acids Biopsy Blood specimen Cardiovascular system Cell Adhesion Molecules Chronic Complex Coronary Coronary heart disease Development Diabetes Mellitus Disease Progression Epidemic Event Fasting Fatty Acids Fish Oils Generations Genes Health Benefit Heart Diseases Human Hyperglycemia In Vitro Incidence Inflammation Inflammatory Insulin Insulin Resistance Interleukin-6 Life Lipids Literature Measures Mediating Mediator of activation protein Membrane Metabolic syndrome Molecular Weight Muscle Muscle Cells Non-Insulin-Dependent Diabetes Mellitus Nuclear Hormone Receptors Obesity Omega-3 Fatty Acids Organ PPAR gamma Parents Peripheral Peroxisome Proliferator-Activated Receptors Pharmaceutical Preparations Process Production Property Protein Isoforms Proteins Rattus Reactive Oxygen Species Risk Factors Series Serum Signal Transduction Source Syndrome TNF gene TNFRSF1A gene Thiazolidinediones Translational Research Triglycerides Tumor Necrosis Factor-alpha Western World adiponectin carbohydrate metabolism cytokine feeding high risk immunoregulation improved inflammatory marker inhibitor/antagonist insulin secretion insulin sensitivity insulin signaling lipid metabolism macrophage oxidation receptor research study response toll-like receptor 4

项目摘要

Obesity and type 2 diabetes are conditions characterized by a state of chronic, low-grade inflammation, due largely to an increase in adipose tissue inflammation brought about by infiltrating macrophages. Drugs such as thiazolidinediones (TZDs) improve insulin sensitivity via activation of PPAR-gamma, and there is much evidence that PPARγ agonists also have anti-inflammatory properties. In addition to their beneficial effects on serum lipids and heart disease, fish oils (ω-3 fatty acids) activate PPARγ and demonstrate antiinflammatory properties. This is a translational research study intended to examine the mechanism for many of the beneficial effects of fish oils on metabolic syndrome in humans. We plan to treat insulin resistant subjects with fish oils and the following hypotheses. Hypothesis 1. The treatment of insulin resistant subjects with fish oils will reduce adipose tissue inflammation. We plan to examine the circulating levels of cytokines, as well as the levels of cytokines and macrophages in adipose tissue biopsies of subjects who are treated with 4 g/day of ω-3 fatty acids for 12 weeks. We will determine whether there is evidence of macrophage apoptosis in adipose tissue, and we will determine whether ω-3 fatty acids increases the level or secretion of adiponectin. Hypothesis 2. Anti-inflammatory effects of fish oils are mediated by activation of PPARγ and/or by changes in membrane composition that affect signal transduction functions. Adipose tissue and macrophages will be treated in vitro with fish oils in the presence and absence of a PPARγ inhibitor, and we will measure PPARγ responses, such as the secretion of HMW adiponectin and macrophage apoptosis. In addition, we will determine whether ω-3 fatty acids induce changes in recruitment of inflammatory receptors, such as toll-like receptor 4 (TLR4) and TNFα Receptor 1 (TNFR1) to membrane rafts. Hypothesis 3. Fish oils improve peripheral insulin sensitivity through a reduction in intramyocellular lipid, and an improvement in muscle insulin signal transduction. Before and after treatment with fish oils, insulin sensitivity will be measured, along with intramyocellular lipid and genes or proteins involved in insulin action and muscle lipid oxidation

肥胖和2型糖尿病是以慢性，低度炎症状态的特征主要是由于浸润巨噬细胞带来的脂肪组织炎症的增加。诸如通过激活PPAR-gamma，噻唑烷二酮（TZD）提高了胰岛素敏感性，并且有很多 PPARγ激动剂也具有抗炎特性的证据。除了它们对血清脂质和心脏病，鱼油（ω-3脂肪酸）激活PPARγ并证明抗炎特性。这是一项翻译研究，旨在检查许多机制鱼油对人类代谢综合征的有益影响。我们计划用鱼油和以下假设。假设1。用鱼油治疗胰岛素耐药受试者将减少脂肪组织炎症。我们计划检查细胞因子的循环水平，以及细胞因子和巨噬细胞的水平用4克/天的ω-3脂肪酸治疗的受试者的脂肪组织活检12周。我们将确定是否存在脂肪组织中巨噬细胞凋亡的证据，我们将确定 ω-3脂肪酸是否会增加脂联素的水平或分泌。假设2。鱼油的抗炎作用是通过PPARγ激活和/或通过变化而介导的影响信号转导功能的膜组成。在存在和不存在PPARγ的情况下，将用鱼油在体外处理脂肪组织和巨噬细胞抑制剂，我们将测量PPARγ反应，例如HMW脂联素和巨噬细胞的分泌凋亡。此外，我们将确定ω-3脂肪酸是否引起募集的变化炎症受体，例如TOLL样受体4（TLR4）和TNFα受体1（TNFR1），向膜筏。假设3。鱼油通过降低细胞内脂质和肌肉胰岛素信号转导的改善。用鱼油处理前后，将测量胰岛素敏感性，以及细胞内脂质以及参与胰岛素作用和肌肉脂质氧化的基因或蛋白质