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: 8329014
• 负责人: Christina Camell
• 金额: $ 3.28万
• 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/8329014
• 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）：在大多数发达国家，肥胖已成为主要的健康风险。在人类和动物模型中的最新研究表明，脂肪组织表现出对青球饮食的炎症反应，其特征是白细胞浸润和炎性细胞因子和趋化因子的表达。这种反应似乎对肥胖症的全身性炎症并发症（例如动脉粥样硬化，代谢综合征和脂肪性肝炎）产生了严重贡献。由于大多数数据来自建立肥胖症后收集的脂肪组织，因此由于高饱和脂肪（HSF）饮食而导致的有关EADY变化的信息很少。在体外，通过用饱和脂肪酸处理激活多种细胞类型，这种反应是通过TLR4和TLR2介导的。三天的HSF饮食会导致鼠脂肪组织的中性粒细胞浸润，而一顿饭会诱导人类的短暂性内毒素血症和白细胞激活。居住在脂肪组织中的白细胞的可能作用和相互作用尚不清楚HSF喂养后的循环。该项目的目的是分析对HSF喂养的非常eady的局部和全身反应，以及启动此响应的细胞。我假设存在于脂肪组织中的白细胞启动时变化，而TLR对于它们的激活是必需的。为了检验该假设，我将在高饱和脂肪进食的鼠模型中检查血液和腹部脂肪组织的分子和细胞变化，并利用TLR4缺乏，TLR2 - / - 和白细胞耗尽的小鼠模型直接解决我的目标。饮食和肥胖症与其他疾病的风险增加，肥胖者的数量增加，包括儿童每年都会增加。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。