Anti-obesity effects of omega 3 fatty acids in brown adipose tissue

棕色脂肪组织中欧米伽 3 脂肪酸的抗肥胖作用

• 批准号: 9171867
• 负责人: Naima Moustaid-Moussa
• 金额: $ 43.46万
• 依托单位: TEXAS TECH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9171867
• 关键词: Address; Adipocytes; Adipose tissue; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Biogenesis; Biological; Body Composition; Body Weight; Body Weights and Measures; Body fat; Brown Fat; Cardiovascular Diseases; Cell Culture Techniques; Cells; Chronic; Data; Diabetes Mellitus; Diet; Dietary Component; Dietary Factors; Dietary Intervention; Eating; Eicosapentaenoic Acid; Energy Metabolism; Epidemic; Exhibits; Fatty Acids; Fatty acid glycerol esters; Food Energy; Gene Expression; Genes; Genotype; Genus Hippocampus; Goals; Health; Health Benefit; Healthcare; Heating; High Fat Diet; Housing; Human; Inflammation; Insulin Resistance; Integrative Medicine; Intervention; Knock-out; Knockout Mice; Link; Mediating; Mesenchymal Stem Cells; Metabolic; Metabolic Diseases; Mission; Mitochondria; Molecular; Morbidity - disease rate; Mus; Nutrient; Obesity; Obesity associated disease; Omega-3 Fatty Acids; Outcomes Research; Physiological; Polyunsaturated Fatty Acids; Prevention; Prevention strategy; Property; Proteins; Public Health; Reducing diet; Reporting; Research; Resistance; Respiration; Risk; Role; Safety; Science; Series; Stem cells; Strategic Planning; Stress; Temperature; Testing; Thermogenesis; Tissues; United States National Institutes of Health; Up-Regulation; abstracting; base; combat; design; dietary supplements; energy balance; evidence base; extracellular; feeding; fibroblast growth factor 21; glucose tolerance; improved; in vivo; innovation; instrument; insulin sensitivity; knock-down; mouse model; natural hypothermia; novel; novel therapeutics; obesity prevention; obesity treatment; prevent; subcutaneous; uncoupling protein 1

Abstract/Summary Obesity increases morbidity risks for several chronic metabolic disorders including diabetes and cardiovascular disease, and has been linked to both systemic and white adipose tissue inflammation. Brown adipose tissue (BAT), a fat tissue which protects against hypothermia, represents a novel target to reduce obesity-associated metabolic disorders. The goal of this proposal is to test whether dietary omega-3 fatty acids (namely eicosapentaenoic acid, EPA) with known anti-inflammatory effects potentially reduce high fat associated adiposity and metabolic alterations via activation of brown fat. We previously demonstrated that EPA-enriched high-fat diets significantly reduced diet-induced obesity, insulin resistance, and inflammation to levels comparable to those in low-fat-fed mice. Furthermore, our recent preliminary data show that these EPA-fed mice also manifest significantly higher brown fat UCP1 protein levels (i.e., uncoupling protein, a BAT-specific thermogenic marker) along with significant increases in gene expression for other markers of thermogenesis. Given the emerging role of BAT in human studies, it is critical to understand how bioactive dietary components such as EPA activate BAT. We hypothesize that the beneficial metabolic effects of EPA in obesity are in part mediated through increasing BAT thermogenic capacity (via upregulation of UCP1) and induction of master regulators of thermogenesis. This hypothesis will be tested in two specific aims through a series of integrated cellular, molecular and physiological studies using mouse models, cultured adipocytes (white and brown) and human mesenchymal stem cells. In aim 1 we will determine in vivo the mechanisms mediating beneficial effects of EPA in BAT and other depots in high-fat-fed wild type and UCP1 knockout mice. In aim 2, using white and brown adipose stem cells derived from animals in aim 1, and human mesenchymal stem cells treated with EPA, we will further dissect the molecular mechanisms by which EPA activates BAT and thermogenic markers (such as UCP1 and PGC1alpha). One of the major outcomes of this research is to provide science-based evidence for potential use of omega-3 fatty acids for improving metabolic health and possibly preventing and/or treating obesity. In addition, we will elucidate mechanisms mediating activation of brown fat by a safe dietary intervention with other proven health benefits. Our studies are consistent with the NIH Strategic Plan for Obesity Research and NCCIH mission emphasizing science-based information to support the usefulness and safety of complementary and integrative health interventions to improve health and health care. The proposed studies are highly innovative and are expected to impact obesity treatment and prevention strategies.

摘要/概要 肥胖增加了几种慢性代谢紊乱的发病风险，包括糖尿病和糖尿病。 心血管疾病，并且与全身性和白色脂肪组织炎症有关。 棕色脂肪组织（BAT）是一种防止体温过低的脂肪组织，代表了一种新的靶点， 减少肥胖相关的代谢紊乱。这项提案的目的是测试饮食是否 已知具有抗炎作用的ω-3脂肪酸（即二十碳五烯酸，EPA） 通过激活棕色脂肪潜在地减少高脂肪相关的肥胖和代谢改变。我们 先前证明富含EPA的高脂肪饮食显著降低了饮食诱导的肥胖， 胰岛素抵抗和炎症的水平与低脂肪喂养的小鼠相当。而且我们的 最近的初步数据表明，这些EPA喂养的小鼠也表现出显着较高的棕色脂肪， UCP 1蛋白水平（即，解偶联蛋白，一种BAT特异性产热标记物）沿着显著的 其他产热标志物的基因表达增加。鉴于最佳可得技术在以下方面的作用日益显现， 在人类研究中，了解EPA等生物活性膳食成分如何激活BAT至关重要。 我们推测EPA在肥胖中的有益代谢作用部分是通过 通过增加BAT产热能力（通过UCP 1的上调）和诱导主 产热的调节剂。这一假设将在两个具体目标通过一系列测试， 使用小鼠模型、培养的脂肪细胞（白色）、 和棕色）和人类间充质干细胞。在目标1中，我们将在体内确定 介导EPA在BAT和其他仓库中对高脂饲养野生型和UCP 1敲除的有益作用 小鼠在aim 2中，使用来源于aim 1中的动物和人的白色和棕色脂肪干细胞， 间充质干细胞与EPA处理，我们将进一步剖析分子机制， EPA激活BAT和产热标志物（如UCP 1和PGC 1 α）。的一个主要 这项研究的结果是为omega-3脂肪酸的潜在用途提供科学依据 用于改善代谢健康并可能预防和/或治疗肥胖。此外，我们将 阐明机制介导激活棕色脂肪的安全饮食干预与其他证明 健康福利。我们的研究与NIH肥胖研究战略计划和NCCIH一致 使命：强调以科学为基础的信息，以支持 和综合卫生干预措施，以改善健康和保健。研究建议高度 创新，预计将影响肥胖治疗和预防策略。