Effects of fish oil on inflammation and metabolic syndrome

鱼油对炎症和代谢综合征的影响

• 批准号: 7613336
• 负责人: Philip A Kern
• 金额: $ 32.84万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7613336
• 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; Research; Risk Factors; Series; Serum; Signal Transduction; Source; Syndrome; TNF gene; Thiazolidinediones; Translational Research; Triglycerides; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Western World; adiponectin; carbohydrate metabolism; cytokine; feeding; high risk; immunoregulation; improved; inflammatory marker; inhibitor/antagonist; insulin secretion; insulin sensitivity; insulin signaling; macrophage; oxidation; receptor; research study; response; toll-like receptor 4

DESCRIPTION (provided by applicant): 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 PPAR3 agonists also have anti-inflammatory properties. In addition to their beneficial effects on serum lipids and heart disease, fish oils (I-3 fatty acids) activate PPAR3 and demonstrate anti-inflammatory 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 I-3 fatty acids for 12 weeks. We will determine whether there is evidence of macrophage apoptosis in adipose tissue, and we will determine whether I-3 fatty acids increases the level or secretion of adiponectin. Hypothesis 2. Anti-inflammatory effects of fish oils are mediated by activation of PPAR3 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 PPAR3 inhibitor, and we will measure PPAR3 responses, such as the secretion of HMW adiponectin and macrophage apoptosis. In addition, we will determine whether I-3 fatty acids induce changes in recruitment of inflammatory receptors, such as toll-like receptor 4 (TLR4) and TNF1 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. Project Narrative: The incidence of obesity, metabolic syndrome, and diabetes is rising in epidemic proportions in the Western world, and the resultant heart disease will likely create a generation who will not live as long as their parents. Fish oils have proven health benefits on coronary risk factors, and this study aims to develop evidence for additional properties of fish oils that will greatly extend their use to subjects with insulin resistance and metabolic syndrome.

描述（由申请人提供）：肥胖和2型糖尿病的疾病是特征的，其特征是慢性，低度炎症状态，这主要是由于浸润性巨噬细胞引起的脂肪组织炎症的增加。胆固醇二酮（TZD）等药物通过激活PPAR-gamma提高胰岛素敏感性，并且有很多证据表明PPAR3激动剂也具有抗炎特性。除了对血清脂质和心脏病的有益作用外，鱼油（I-3脂肪酸）激活了PPAR3并表现出抗炎特性。这是一项翻译研究，旨在研究鱼油对人类代谢综合征的许多有益作用的机制。我们计划用鱼油和以下假设来治疗耐胰岛素的受试者。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，以及脂肪组织活检中的细胞因子和巨噬细胞的水平，这些受试者的受试者活检，这些受试者用4克/天的I-3脂肪酸治疗，持续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I-3脂肪酸是否会增加脂联素的水平或分泌。假设2。鱼油的抗炎作用是由PPAR3激活和/或通过影响信号转导功能的膜组成的变化来介导的。在存在和不存在PPAR3抑制剂的情况下，将用鱼油在体外处理脂肪组织和巨噬细胞，我们将测量PPAR3反应，例如HMW脂联素和巨噬细胞凋亡的分泌。此外，我们将确定I-3脂肪酸是否诱导炎症受体的募集变化，例如Toll样受体4（TLR4）和TNF1受体1（TNFR1）对膜筏。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来改善周围胰岛素敏感性。在用鱼油处理前后，将测量胰岛素敏感性，以及胰岛素作用和肌肉脂质氧化的基因或蛋白质的基因或蛋白质。 项目叙述：肥胖，代谢综合征和糖尿病的发生率在西方世界的流行比例上升，由此产生的心脏病可能会产生一代人，只要他们的父母就不会生存。鱼油已证明对冠状动脉危险因素具有健康益处，这项研究旨在为鱼油的其他特性开发证据，这些证据将大大扩展其使用胰岛素抵抗和代谢综合征的受试者。