EFFECTS OF FISH OIL AND ALPHA-LIPOIC ACID ON THE PROGR OF INSUL RESIST

鱼油和硫辛酸对胰岛素抵抗进程的影响

• 批准号: 8172550
• 负责人: PETER J HAVEL
• 金额: $ 11.41万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172550
• 关键词: Adhesions; Antioxidants; Apolipoproteins B; Attention; Attenuated; Beta Cell; Body fat; C-reactive protein; Characteristics; Computer Retrieval of Information on Scientific Projects Database; Development; Diet; Dyslipidemias; Ensure; Fish Oils; Functional disorder; Funding; Grant; High Density Lipoproteins; Homocysteine; Homocystine; Human; Hypertriglyceridemia; Incidence; Inflammation; Inflammatory; Institution; Insulin Resistance; Intake; Interleukin-6; Lipids; Lipoproteins; Long-Term Effects; Macaca mulatta; Metabolic Diseases; Metabolic syndrome; Modeling; Monocyte Chemoattractant Protein-1; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oxidative Stress; PPAR alpha; Particle Size; Plasma; Plasminogen Activator Inhibitor 1; Prevalence; Primary Prevention; Research; Research Personnel; Resources; Source; Supplementation; Testing; Thioctic Acid; Tumor Necrosis Factor-alpha; United States National Institutes of Health; Weight; adiponectin; cardiovascular risk factor; dietary supplements; moderate obesity; nonhuman primate; oxidation; prevent; sugar; sweetened beverage

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The prevalence of obesity is increasing markedly. Even moderate obesity can contribute to the development of the pathological characteristics of the Metabolic Syndrome. Insulin resistance is the underlying characteristic of Metabolic Syndrome and, along with beta-cell dysfunction, results in Type 2 Diabetes Mellitus (T2DM). Due to the rising incidence of Metabolic Syndrome and T2DM and the limited ability of current treatments to prevent their long-term complications, it is clear that more attention needs to be focused on primary prevention of insulin resistance. In this application we propose to investigate the long-term (1 year) effects of fish oil and ¿-lipoic acid supplementation, alone and in combination, to prevent or attenuate the progression of insulin resistance and dyslipidemia in a nonhuman primate model of diet-induced insulin resistance. The development of insulin resistance in obese rhesus monkeys shares similar features with the progression of metabolic disease in humans. We have previously demonstrated that providing obese rhesus monkeys with a sugar-sweetened beverage daily in combination with ad libitum access to their normal diet for 1 year results in modest weight and body fat gain accompanied by a rapid progression of insulin resistance and dyslipidemia (elevated triglyceride and reduced HDL levels). The use of this model in which rigorous control and compliance with diet and supplement intake can be ensured will allow us to determine the effects of long-term administration of fish oil and ¿-lipoic acid on the progression of thedevelopment and progression of insulin resistance and dyslipidemia. We propose to determine the efficacy of two widely used nutritional supplements known to activate PPARs and/or target lipid dysregulation, inflammation (fish oil), and oxidative stress (alpha-lipoic acid) in this nonhuman primate model. We will pursue the following specific aims: Specific Aim 1: Test the hypothesis that supplementation with fish oil will activate PPARalpha, gamma and delta, increase plasma adiponectin levels, and prevent or attenuate the progression of insulin resistance. Specific Aim 2: Test the hypothesis that supplementation with the potent anti-oxidant, alpha-lipoic acid will reduce oxidative stress and prevent or attenuate the progression of insulin resistance. Specific Aim 3: Test the hypothesis that the effects fish oil in combination with alpha-lipoic acid will be greater than either fish oil or alpha-lipoic acid alone. In addition, we will determine the effects of the supplements on lipid, oxidative stress and inflammatory parameters associated with insulin resistance and cardiovascular risk including substrate oxidation, apolipoprotein-B, lipoprotein particle size, adiponectin, C-reactive protein, homocysteine, interleukin-6, tumor necrosis factor-alpha, monocyte-chemoattractant protein-1, soluble adhesion factors, and PAI-1.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 肥胖的患病率越来越明显。即使是现代肥胖也可以有助于代谢综合征的病理特征的发展。胰岛素抵抗是代谢综合征的潜在特征，并且与β细胞功能障碍一起导致2型糖尿病（T2DM）。由于代谢综合征和T2DM的增加，以及当前治疗能够防止其长期并发症的能力有限，很明显，更多的关注需要集中在胰岛素抵抗的一级预防上。在此应用中，我们建议研究鱼油和 - 单独和组合补充鱼油的长期（1年）影响，以预防或减弱饮食诱导的胰岛素耐药性的非人类私有模型中胰岛素抵抗和血脂异常的进展。肥胖恒河猴中胰岛素抵抗的发展与人类代谢疾病的发展具有相似的特征。我们先前已经证明，每天提供肥胖的恒河猴每天提供糖味的勃乳，并随意获得其正常饮食的1年，从而导致体重适度和体内脂肪的增加，从而通过胰岛素耐药性的快速进展和发热性疾病（触发触发症状升高）和降低的HDL水平）。使用这种模型的使用，可以确保严格控制和遵守饮食和补充摄入量将使我们能够确定鱼油长期给药的影响以及lipoii酸对胰岛素抵抗和血脂异常的发展和进展的影响。我们建议在此非人类私有模型中确定已知的两种已知可激活PPAR和/或靶脂质失调，感染（鱼油）和氧化应激（α-丝酸）的营养补充剂的效率。我们将追求以下特定目的：特定目标1：测试以下假设：补充鱼油将激活pparalpha，伽马和三角洲，增加血浆脂联素水平，并防止或防止或防止胰岛素耐药性的进展。具体目的2：检验以下假设：补充潜在的抗氧化剂，α-脂肪酸将减少氧化应激，并防止或防止胰岛素抵抗的进展。具体目的3：检验假设，即鱼油与α-脂肪酸结合使用的效果将大于单独的鱼油或α-脂酸。 In addition, we will determine the effects of the supplements on lipid, oxidative stress and inflammatory parameters associated with insulin resistance and cardiovascular risk including substrate oxidation, apolipoprotein-B, lipoprotein particle size, adiponectin, C-reactive protein, homocysteine, interleukin-6, tumor necrosis factor-alpha, monocyte-chemoattractant蛋白-1，固体粘附因子和PAI-1。