Conjugated linoleic acid (CLA) promotes inflammation in human adipocytes

共轭亚油酸（CLA）促进人类脂肪细胞炎症

基本信息

批准号：
7907519
负责人：
Kristina Brooke Martinez-Guryn
金额：
$ 2.85万
依托单位：
UNIVERSITY OF NORTH CAROLINA GREENSBORO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-13 至 2011-07-12
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7907519
关键词：
ATF2 gene Adipocytes Adipose tissue Adult Adverse effects Animals Apoptosis Attenuated Blood Vessels Body Weight Body Weight decreased Body fat Cardiovascular Diseases Cell Line Cell Separation Cell model Cells Chemicals Chemotactic Factors Chronic Disease Coculture Techniques Conditioned Culture Media Conjugated Linoleic Acids Cytokine Gene Data Diabetes Mellitus Disease Endocrine Experimental Models Exposure to FOS gene Fatty Acids Figs - dietary Fortified Food GLUT4 gene Gene Expression Gene Targeting Genes Glucose Goals Health Health Care Costs Healthcare Human Hypertension IL8 gene Inflammation Inflammatory Inflammatory Response Insulin Insulin Resistance Interleukin-1 Isomerism JUN gene Knowledge Lead Link Lipolysis MAPK14 gene MAPK7 gene Maintenance Measures Mediating Mediator of activation protein Metabolic Metabolism Mitogen-Activated Protein Kinases Modeling NF-kappa B Non-Insulin-Dependent Diabetes Mellitus Obesity Obesity associated disease Outcome PTGS2 gene Pathway interactions Peroxisome Proliferators Pharmaceutical Preparations Phosphotransferases Population Prevalence Production Prostaglandin-Endoperoxide Synthase Prostaglandins Protein Kinase Proteins Public Health Reporting Research Risk Role Safety Signal Pathway Signal Transduction Small Interfering RNA Testing Transcription Factor AP-1 Triglycerides Weight maintenance regimen Work activating transcription factor 3 adiponectin attenuation base cell type cytokine dietary supplements direct application improved inhibitor/antagonist innovation insulin signaling lipid biosynthesis lipid metabolism mixed lineage kinase 3 monocyte nutrition protein activation receptor response stress-activated protein kinase 1 upstream kinase uptake

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of this research is to identify safe and effective dietary strategies to reduce the prevalence of obesity and associated diseases. One potential anti-obesity compound is conjugated linoleic acid (CLA), sold woridwide for weight loss. However, several adverse side effects have been reported in animals and humans such as hyperiipidemia, inflammation, and insulin resistance. Therefore, the safety of this supplement remains questionable. Furthermore, the specific cell type(s) in white adipose tissue (WAT) responsible for initiating an inflammatory response to CLA treatment, and the mechanism by which 10,12 CLA promotes delipidation, are unknown. Therefore, the specific aims of this proposal are to 1) determine which cell type in WAT (i.e., the preadipocyte or the adipocyte) that is the major mediator of 10,12 CLA- mediated inflammation, insulin resistance, and delipidation in primary cultures of newly differentiated human adipocytes, and 2) to identify the specific mechanism(s) involved. Based on my preliminary data, it is expected in Aim #1 that adipocytes are the major instigators of 10,12 CLA-induced inflammation, insulin resistance, and delipidation. It is anticipated in Aim #2 that 10,12 CLA mediates these effects through activating activator protein (AP)-1 via upstream activation of mitogen activated protein kinases (MAPKs). To complete the proposed studies in Aim #1, four different experimental models will be employed to determine whether the preadipocyte or the adipocyte is responsible for 10,12 CLA-mediated inflammation, insulin resistance, and delipidation. In Aim #2, chemical inhibitors and siRNA will be used to determine the role of upstream MAPKs and AP-1 in mediating 10,12 CLA-induced inflammatory gene expression, insulin resistance, and delipidation. Inflammation will be examined by measuring inflammatory gene expression, protein activation, and secretion of adipocytokines and prostaglandins into the media. Insulin resistance will be determined by measuring insulin-stimulated glucose and fatty acid uptake. The rationale for the proposed research is that once we understand which cells in WAT trigger the inflammatory response by CLA and how this occurs, it's safe use as a dietary approach for weight control can be evaluated effectively. The proposed research is important to public health, because it will provide information needed to identify safe and effective dietary strategies to reduce body fat and improve overall health. The improvement of overall health is expected to reduce the amount of money spent on medications and health care needed for treating obesity and diabetes.

描述（由申请人提供）：这项研究的长期目标是确定安全有效的饮食策略，以减少肥胖症和相关疾病的患病率。一种潜在的抗肥胖化合物是共轭亚油酸（CLA），出售了可减肥的范围。然而，已经报道了动物和人类的几种不良副作用，例如高脂肪血症，炎症和胰岛素抵抗。因此，这种补充的安全仍然值得怀疑。此外，负责对CLA治疗产生炎症反应的白色脂肪组织（WAT）中的特定细胞类型以及10,12 CLA促进删除的机制未知。因此，该提案的具体目的是1）确定WAT中的哪种细胞类型（即前脂肪细胞或脂肪细胞）是10,12个cla介导的炎症，胰岛素抵抗，胰岛素抵抗的主要介体，以及在新差异化的人脂肪中的原发性培养物中的特定机制，以及确定特定机构的新原代培养物。基于我的初步数据，预计AIM＃1可以是脂肪细胞是10,12个CLA诱导的炎症，胰岛素抵抗和磨难的主要启动者。在AIM＃2中预计，10,12 CLA通过激活蛋白（AP）-1通过有丝分裂原活化蛋白激酶（MAPK）的上游激活介导了这些作用。为了在AIM＃1中完成拟议的研究，将采用四个不同的实验模型来确定前脂肪细胞或脂肪细胞是否负责10,12 CLA介导的炎症，胰岛素抵抗和删除。在AIM＃2中，化学抑制剂和siRNA将用于确定上游MAPK和AP-1在介导10,12个CLA诱导的炎症基因表达，胰岛素抵抗和删除方面的作用。通过测量炎症基因表达，蛋白质激活以及将脂肪细胞因子和前列腺素的分泌来检查炎症。胰岛素抵抗将通过测量胰岛素刺激的葡萄糖和脂肪酸摄取来确定。拟议的研究的理由是，一旦我们了解了WAT中哪些细胞触发CLA的炎症反应，以及如何进行这种情况，它可以安全地用作体重控制的饮食方法。拟议的研究对公共卫生很重要，因为它将提供所需的信息来确定安全有效的饮食策略，以减少体内脂肪并改善整体健康状况。预计整体健康状况的改善将减少用于治疗肥胖和糖尿病所需的药物和医疗保健所花费的金额。