Dietary fat, visceral fat depots and aging

我们研究的长期目标是确定内脏脂肪对胰岛素敏感性的影响， 中心blog上个世纪医疗保健的改善显著延长了平均寿命 在发达国家。随着老年人口的增长，医生正在治疗更多的老年人。 患有与年龄有关的疾病的患者。代谢综合征、动脉粥样硬化 疾病，胰岛素抵抗和糖尿病-从7%跃升至近20%的人口后， 75岁-挑战全球医学界。影响胰岛素抵抗的两个因素 和糖尿病是缺乏体育活动和不健康的饮食，两者结合可能导致肥胖。 对小鼠和大鼠的几项研究表明，肥胖会导致胰岛素抵抗，并对胰岛素抵抗有负面影响。 中心blog热量限制减少脂肪的体积，提高胰岛素敏感性和延长寿命。 人们可以推断，一个瘦的身体促进健康的胰岛素作用和更长的寿命。然而，艾姆斯矮， GHRKO小鼠对注射的胰岛素高度敏感，尽管体积增加或正常， 脂肪（取决于年龄）。是什么调节了这些突变动物的高胰岛素敏感性和更长的寿命？ 我们假设Prop 1df突变和GHR敲除导致白色脂肪细胞中有益的改变， 影响胰岛素敏感性和寿命的组织。 在本研究中，我们将研究高脂饮食和内脏脂肪库对胰岛素的影响 正常、艾姆斯侏儒和GHRKO小鼠的信号传导和寿命。我们认为长寿的艾姆斯会使人矮小， GHRKO小鼠将对HFD的有害作用具有抗性。同时根据我们的初步数据显示 在GHRKO和艾姆斯中，内脏脂肪在胰岛素信号调节中的作用非常不同，几乎相反 侏儒小鼠与正常动物相比，我们认为内脏脂肪去除不会提高胰岛素 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 信号和寿命。建议的具体目标如下： 目的1：分析内脏脂肪库切除术与基因型对胰岛素的交互作用 GHRKO、艾姆斯侏儒小鼠和正常小鼠中的信号传导、脂肪细胞因子、脂质代谢和寿命。 目的2：分析高脂饮食（HFD）对胰岛素信号传导、脂肪细胞因子、细胞因子、脂质和 GHRKO、艾姆斯侏儒和正常小鼠中的代谢。 目的3：确定在体内生长激素对胰岛素信号传导作用缺乏的情况下内脏脂肪的功能 将GHRKO的内脏脂肪移植到正常小鼠体内。

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.