Early inflammatory responses to high saturated fat diet

高饱和脂肪饮食的早期炎症反应

• 批准号: 8025921
• 负责人: Christina Camell
• 金额: $ 3.2万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-21 至 2013-09-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8025921
• 关键词: Acids; Address; Adipose tissue; Animal Model; Atherosclerosis; Blood; Blood Circulation; CCL2 gene; Cells; Child; Data; Developed Countries; Diet; Disease; Endotoxemia; Exhibits; Gene Expression; Goals; Health; Human; In Vitro; Infiltration; Inflammatory; Inflammatory Response; Intercellular adhesion molecule 1; Interleukin-6; Intra-abdominal; Leukocytes; Lymph; Mediating; Metabolic syndrome; Modeling; Molecular; Mononuclear; Mus; Neutrophil Infiltration; Obesity; Phagocytes; Risk; Role; Saturated Fatty Acids; Steatohepatitis; TLR2 gene; TLR4 gene; Testing; cell type; chemokine; cytokine; feeding; leukocyte activation; lymph nodes; macrophage; mouse model; neutrophil; obesogenic; response; saturated fat

DESCRIPTION (provided by applicant): Obesity has become a major health risk in most developed countries. Recent studies in humans and animal models have shown adipose tissue to exhibit an inflammatory response to obesigenic diets that is characterized by infiltration of leukocytes and expression of inflammatory cytokines and chemokines. This response appears to contribute critically to the systemic inflammatory complications of obesity such as atherosclerosis, metabolic syndrome and steatohepatitis. Since most of the data comes from adipose tissues collected after obesity is established, there is little information available on the eady changes as a result of high saturated fat (HSF) diet. In vitro a variety of cell types are activated by treatment with saturated fatty-acids and this response is mediated through TLR4 and TLR2. Three days of HSF diet results in neutrophil infiltration of murine adipose tissues, and a single meal induces transient endotoxemia and leukocyte activation in humans. The possible roles and interaction of leukocytes resident in adipose tissue and in circulation following HSF feeding are unclear. The goal of this project is to analyze the very eady local and systemic response to HSF feeding and the cells which initiate this response. I hypothesize that leukocytes resident in the adipose tissue initiate eady changes and TLRs are necessary for their activation. To test this hypothesis I will examine molecular and cellular changes in the blood and intra- abdominal adipose tissue in a murine model of high saturated fat feeding and utilize the TLR4 deficient, TLR2-/- and leukocyte depleted mouse models to directly address my aims. There is a high association of diet and obesity with increased risk for other diseases and the number of obese persons, including children grows larger every year. It is necessary to understand the different factors that contribute to this risk, including the immediate response to a high saturated fat diet.

描述（由申请人提供）：肥胖已成为大多数发达国家的主要健康风险。最近对人类和动物模型的研究表明，脂肪组织对致肥胖饮食表现出炎症反应，其特征是白细胞浸润以及炎症细胞因子和趋化因子的表达。这种反应似乎对肥胖引起的全身炎症并发症如动脉粥样硬化、代谢综合征和脂肪性肝炎有重要影响。由于大部分数据来自肥胖形成后收集的脂肪组织，因此关于高饱和脂肪（HSF）饮食导致的快速变化的信息很少。在体外，多种细胞类型通过饱和脂肪酸处理被激活，并且这种反应是通过 TLR4 和 TLR2 介导的。三天的 HSF 饮食会导致小鼠脂肪组织中性粒细胞浸润，单餐会导致人类短暂的内毒素血症和白细胞活化。 HSF 喂养后，驻留在脂肪组织和循环中的白细胞的可能作用和相互作用尚不清楚。该项目的目标是分析对 HSF 喂养的非常迅速的局部和全身反应以及启动这种反应的细胞。我假设脂肪组织中的白细胞会引发快速变化，而 TLR 是其激活所必需的。为了检验这一假设，我将在高饱和脂肪喂养的小鼠模型中检查血液和腹内脂肪组织的分子和细胞变化，并利用 TLR4 缺陷、TLR2-/- 和白细胞耗尽的小鼠模型来直接实现我的目标。饮食和肥胖与其他疾病的风险增加密切相关，并且肥胖者（包括儿童）的数量每年都在增加。有必要了解导致这种风险的不同因素，包括对高饱和脂肪饮食的立即反应。