Dietary fat, visceral fat depots and aging

膳食脂肪、内脏脂肪库和衰老

• 批准号: 8536984
• 负责人: MICHAL Mateusz MASTERNAK
• 金额: $ 4.38万
• 依托单位: UNIVERSITY OF CENTRAL FLORIDA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8536984
• 关键词: Adipocytes; Adipose tissue; Affect; Age; Aging; Animals; Body Weight; Body fat; Caloric Restriction; Communities; Data; Developed Countries; Diabetes Mellitus; Diet; Dietary Fats; Disease; Elderly; Environment; Excision; Fatty acid glycerol esters; Food; Genetic; Genotype; Glucose; Goals; Growth Hormone Receptor; Healthcare; Human; Incidence; Infiltration; Insulin; Insulin Resistance; Knock-out; Knockout Mice; Laboratories; Life; Life Style; Liver; Longevity; Medical; Metabolic syndrome; Mus; Mutation; Obesity; Operative Surgical Procedures; Organ; Pathology; Patients; Perception; Physical activity; Physicians; Population; Predisposition; Production; Publishing; Race; Rattus; Regimen; Regulation; Research; Resistance; Review Literature; Role; Siblings; Signal Transduction; Skeletal Muscle; Testing; Tissues; Transplantation; Visceral; Work; adiponectin; age related; base; cytokine; diabetic; fasting glucose; glucose tolerance; improved; in vivo; insulin sensitivity; insulin signaling; lipid metabolism; mutant; research study; response; somatotropin-binding protein; subcutaneous

The long-term goal of our research is to determine the effects of visceral fat on insulin sensitivity and longevity. Improvements in healthcare during the last century have significantly increased the average lifespan in developed countries. With the growing population of elderly, physicians are treating a greater number of patients suffering from age-related diseases. Growing incidence of metabolic syndrome, atherosclerotic disease, insulin resistance and diabetes mellitus-which jumps from 7% to almost 20% of the population after age 75-challenges the global medical community. Two well-documented factors affecting insulin resistance and diabetes are a lack of physical activity and an unhealthy diet, which may cause obesity when combined. Several studies with mice and rats indicated that obesity causes insulin resistance and has negative effects on longevity. Calorie restriction decreases the volume of fat, improves insulin sensitivity and extends longevity. One could infer that a lean body promotes healthy insulin action and a longer life. However, Ames dwarf and GHRKO mice are both hyper-sensitive to injected insulin and long-lived despite an increased or normal volume of fat (depending on age). What regulates high insulin sensitivity and longer lifespan in these mutant animals? We hypothesize that Prop1df mutation and GHR knockout cause beneficial alterations in white adipose tissue that influences insulin sensitivity and longevity. In the proposed studies, we will investigate effects of a high fat diet (HFD) and visceral fat depots on insulin signaling and longevity in normal, Ames dwarf and GHRKO mice. We propose that long-living Ames dwarf and GHRKO mice will be resistant to the detrimental effects of HFD. Also based on our preliminary data indicating a very different, nearly opposite role of visceral fat in the regulation of insulin signaling in GHRKO and Ames dwarf mice in comparison to normal animals, we propose that visceral fat removal will not improve insulin action and longevity of these long-lived mutants. We believe that these studies will elucidate the interaction of visceral fat depots and diet on insulin signaling and longevity. The following specific aims are proposed: Aim 1: Analyze the interactive effects of surgical removal of visceral fat depots and genotype on insulin signaling, adipocytokines, lipid metabolism and longevity in GHRKO, Ames dwarf and normal mice. Aim 2: Analyze the effects of a high fat diet (HFD) on insulin signaling, adipocytokines, cytokines, lipid and metabolism in GHRKO, Ames dwarf and normal mice. Aim 3: Determine the function of visceral fat developed in the absence of GH action on insulin signaling in vivo by transplanting visceral fat from GHRKO into normal mice.

我们研究的长期目标是确定内脏脂肪对胰岛素敏感性和胰岛素敏感性的影响。 长寿。上个世纪医疗保健的进步显着延长了平均寿命 在发达国家。随着老年人口的不断增加，医生正在治疗越来越多的患者 患有与年龄有关的疾病的患者。代谢综合征、动脉粥样硬化的发病率不断上升 疾病、胰岛素抵抗和糖尿病——此后该人群的比例从 7% 跃升至近 20% 75岁——挑战全球医学界。影响胰岛素抵抗的两个有据可查的因素 而糖尿病则是缺乏体力活动和不健康饮食，两者结合起来可能会导致肥胖。 几项针对小鼠和大鼠的研究表明，肥胖会导致胰岛素抵抗，并对身体产生负面影响。 长寿。热量限制可以减少脂肪体积，提高胰岛素敏感性并延长寿命。 人们可以推断，瘦身可以促进健康的胰岛素作用并延长寿命。然而，艾姆斯矮星和 GHRKO 小鼠对注射的胰岛素高度敏感，并且尽管体积增加或正常，但仍寿命较长 脂肪（取决于年龄）。是什么调节这些突变动物的高胰岛素敏感性和更长的寿命？ 我们假设 Prop1df 突变和 GHR 敲除会导致白色脂肪发生有益的改变 影响胰岛素敏感性和寿命的组织。 在拟议的研究中，我们将研究高脂肪饮食 (HFD) 和内脏脂肪库对胰岛素的影响 正常小鼠、艾姆斯侏儒小鼠和 GHRKO 小鼠的信号传导和寿命。我们建议长寿的艾姆斯矮人和 GHRKO 小鼠能够抵抗 HFD 的有害影响。还根据我们的初步数据表明 内脏脂肪在 GHRKO 和 Ames 胰岛素信号调节中的作用非常不同，几乎相反 与正常动物相比，侏儒小鼠，我们认为去除内脏脂肪不会改善胰岛素 这些长寿突变体的作用和寿命。 我们相信这些研究将阐明内脏脂肪库和饮食对胰岛素的相互作用 信号传递和寿命。提出以下具体目标： 目标 1：分析手术切除内脏脂肪库和基因型对胰岛素的交互影响 GHRKO、艾姆斯侏儒小鼠和正常小鼠的信号传导、脂肪细胞因子、脂质代谢和寿命。 目标 2：分析高脂饮食 (HFD) 对胰岛素信号、脂肪细胞因子、细胞因子、脂质和 GHRKO、Ames 侏儒小鼠和正常小鼠的代谢。 目标 3：确定 GH 对体内胰岛素信号传导缺乏作用时形成的内脏脂肪的功能 通过将 GHRKO 的内脏脂肪移植到正常小鼠体内。