Metabolic Actions of Omega-3 Fatty Acids on Inflammation

Omega-3 脂肪酸对炎症的代谢作用

• 批准号: 8275681
• 负责人: ANDREW P GOLDBERG
• 金额: $ 15.62万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8275681
• 关键词: Abdomen; Abdominal Muscles; Acids; Acute-Phase Proteins; Adipocytes; Adipose tissue; Adult; Affect; Anti-Inflammatory Agents; Anti-inflammatory; Biological Markers; Blood Pressure; Body Composition; Cardiovascular Diseases; Central obesity; Characteristics; Cholesterol Esters; Clinical; Clinical Research; Collaborations; Comparative Study; Deposition; Dual-Energy X-Ray Absorptiometry; Epidemic; Epidemiologic Studies; Fasting; Fatty acid glycerol esters; Fish Oils; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Hip region structure; Human; Hypertriglyceridemia; Impaired fasting glycaemia; Inflammation; Inflammatory; Insulin; Insulin Resistance; Intra-abdominal; Investigation; Life Style; Linolenic Acids; Lipids; Lipolysis; Lipoproteins; Liver; Macronutrients Nutrition; Marines; Measures; Mediating; Mediator of activation protein; Metabolic; Metabolic syndrome; Metabolism; Methodology; Muscle; National Institute of Diabetes and Digestive and Kidney Diseases; Nonesterified Fatty Acids; Nutraceutical; Nutritional Biochemistry; Obesity; Oils; Omega-3 Fatty Acids; Outcome; Outcome Study; Overweight; Patients; Pharmaceutical Preparations; Physiological; Plasma; Polyunsaturated Fatty Acids; Research; Research Design; Research Personnel; Risk; Supplementation; Therapeutic; Therapeutic Uses; Therapy Clinical Trials; Tissues; Translating; Triglycerides; Viscera; Visceral; Weight; Woman; X-Ray Computed Tomography; abdominal fat; adipocyte biology; alpha-Linolenic Acid; basal insulin; cardiovascular disorder risk; cytokine; efficacy testing; eicosapentanoic acid; experience; glucose tolerance; glycerol-insulin; heart disease risk; improved; insight; insulin sensitivity; lipid biosynthesis; lipid metabolism; macrophage; men; novel; novel strategies; nutrition; paracrine; particle; programs; randomized trial; response; subcutaneous; treatment planning; uptake

DESCRIPTION (provided by applicant): Clinical studies suggest that the marine-derived omega-3 polyunsaturated fatty acids (PUFAs), eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) improve high triglyceride (TG) and blood pressure (BP) constituents of the metabolic syndrome (MetS) , and also reduce cytokines; however, we are not aware of any studies that have examined the mechanisms underlying these effects in overweight men and women with MetS. Of the few human studies evaluating EPA/DHA supplementation on lipid metabolism, most were conducted for short periods in normal weight or non-hyperTG subjects and did not measure effects on adipocyte lipolysis, adipokine secretion, lipogenesis or visceral fat. We hypothesize that EPA/DHA supplementation will not only reduce plasma TG, but also decrease systemic and tissue inflammation, insulin resistance (HOMA-IR), adipose tissue lipolysis and cytokine release to enhance the TG storage capacity of adipose tissue. The reduction in inflammation and increase in insulin sensitivity will remodel adipose tissue to function more efficiently in TG uptake and storage, thus reducing circulating FFAs and cytokines. We further postulate that these metabolic effects may decrease ectopic fat deposition in viscera (intra-abdominal fat and muscle), an intriguing, novel outcome that provides rationale for the 9-month treatment plan. The Aims of this R21 proposal are to conduct a pilot, 9 month randomized trial in adults with MetS comparing the effects of EPA/DHA vs. ALA supplementation on 1) Metabolic (e.g., lipoproteins, inflammatory cytokines, acute phase reactants, glucose tolerance/insulin resistance) and adipose tissue metabolism (basal and insulin suppressed lipolysis (ED50), cytokine release and lipogenesis), and 2) Regional fat distribution quantified as, visceral and subcutaneous adipose volumes and muscle lipid accumulation by CT-scan and body composition (total and regional fat mass) by dual energy absorptiometry (DXA). This proposal capitalizes on collaboration among experienced investigators in lipoprotein metabolism, nutritional biochemistry and adipocyte biology in a NIDDK-Nutrition Obesity Research Center to examine a clinical/therapeutic question using a novel study design and methodologies that will determine the mechanisms by which omega-3 PUFA (EPA, DHA and ALA) supplementation affect adipocyte biology to reduce inflammation, lipolysis, TG and ectopic fat accumulation in adults with MetS. Favorable outcomes could translate into therapeutic trials to test the efficacy of EPA/DHA supplements, either singly or in combination with other drugs to reduce TG, systemic inflammation, insulin resistance and CVD risk. PUBLIC HEALTH RELEVANCE: The metabolic syndrome raises the risk of heart disease and is currently at epidemic proportions in the U.S. It consists of 3 of the following components: central obesity, high triglycerides, low HDL, abnormal blood pressure and impaired fasting glucose levels. Previous studies have suggested that omega-3 fish oil may influence some of these components but the mechanisms involved are not well understood. Therefore, this proposal will investigate how omega-3 fish oils affect inflammation, lipids and fat breakdown by comparing it to a non-fish oil omega-3 supplement (linolenic acid). Favorable outcomes from this study could translate into a new approach to improve heart disease risk in men and women with the metabolic syndrome.

描述（由申请人提供）：临床研究表明，海洋衍生的欧米茄-3多不饱和脂肪酸（PUFAS），eicosapentanoic Acid（EPA）和Docosahecosahexanoic（DHA）改善了高甘油三酸酯（TG）和血压（BP）成分代谢综合征（MetS），还减少细胞因子；但是，我们不知道有任何研究已经检查了超重男女大都会的这些作用的机制。在评估脂质代谢的EPA/DHA补充的少数人类研究中，大多数是在正常体重或非急诊受试者中进行短期进行的，并且没有衡量对脂肪细胞脂肪分解，脂肪因子分泌，脂肪生成或内脏脂肪的影响。我们假设补充EPA/DHA不仅会减少血浆TG，还可以减少全身性和组织炎症，胰岛素抵抗（HOMA-IR），脂肪组织脂肪分解和细胞因子释放，从而增强脂肪组织的TG储存能力。炎症的减少和胰岛素敏感性的增加将重塑脂肪组织，以在TG摄取和储存中更有效地发挥作用，从而减少循环中的FFA和细胞因子。我们进一步假设这些代谢作用可能会降低内脏（腹部脂肪和肌肉）的异位脂肪沉积，这是一个有趣的新型结果，为9个月的治疗计划提供了基本原理。该R21提案的目的是在成年人中进行9个月的随机试验，其中MetS比较了EPA/DHA与补充ALA对1）对1）代谢的影响（例如脂蛋白，炎症细胞因子，急性相反应物，葡萄糖耐受性/胰岛素抵抗）和脂肪组织代谢（基底和胰岛素抑制脂解（ED50），细胞因子释放和脂肪生成），以及2）2）量化的区域脂肪分布，被定量为内脏和皮下脂肪量和皮下脂肪量和肌肉脂质，由CT-SCAN和身体成分（CT-SCAN和身体成分）和区域脂肪质量）通过双能吸收法（DXA）。该提案利用了经验丰富的研究人员在脂蛋白代谢，营养生物化学和脂肪细胞生物学中的合作，在NIDDK-NUTRITION肥胖研究中心，使用新颖的研究设计和方法来研究临床/治疗问题，以确定临床/治疗性问题，从而确定哪种机制的机制。 （EPA，DHA和ALA）补充会影响脂肪细胞生物学，以减少患有MetS的成年人的炎症，脂解，TG和异位脂肪的积累。有利的结果可以转化为治疗试验，以单独或与其他药物结合使用EPA/DHA补充剂的功效，以减少TG，全身性炎症，胰岛素抵抗和CVD风险。 公共卫生相关性：代谢综合征增加了心脏病的风险，目前处于美国的流行比例，包括以下3个成分：中央肥胖症，高甘油三酸酯，低HDL，低HDL，血压异常和禁食葡萄糖水平受损。先前的研究表明，omega-3鱼油可能会影响其中一些组成部分，但涉及的机制尚不清楚。因此，该提案将通过将其与非鱼油omega-3补充剂（亚麻酸）进行比较，研究omega-3鱼油如何影响炎症，脂质和脂肪分解。这项研究的有利结果可以转化为一种新方法，以改善代谢综合征的男性和女性心脏病风险。