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

• 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
• 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

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）：本研究的长期目标是确定安全有效的饮食策略，以减少肥胖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），在全球范围内销售用于减肥。然而，在动物和人类中已经报道了几种不良副作用，例如高脂血症、炎症和胰岛素抵抗。因此，这种补充剂的安全性仍然值得怀疑。此外，白色脂肪组织（WAT）中负责引发对CLA处理的炎症反应的特定细胞类型以及10，12 CLA促进脱脂的机制尚不清楚。因此，该提议的具体目的是1）确定WAT中的哪种细胞类型（即，前脂肪细胞或脂肪细胞），其是新分化的人脂肪细胞的原代培养物中10，12 CLA介导的炎症、胰岛素抗性和脱脂的主要介质，和2）鉴定所涉及的特定机制。基于我的初步数据，预期目标#1中脂肪细胞是10，12 CLA诱导的炎症、胰岛素抵抗和去脂的主要引发者。目标2中预计10，12 CLA通过上游激活有丝分裂原活化蛋白激酶（MAPKs）来激活激活蛋白（AP）-1介导这些作用。为了完成目标#1中提出的研究，将采用四种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、胰岛素抵抗和脱脂。在目标#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 CLA诱导的炎症基因表达、胰岛素抵抗和去脂中的作用。将通过测量炎症基因表达、蛋白质活化以及脂肪细胞因子和胰高血糖素分泌到培养基中来检查炎症。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。这项研究的基本原理是，一旦我们了解了WAT中的哪些细胞触发了CLA的炎症反应以及这种反应是如何发生的，就可以有效地评估它作为控制体重的饮食方法的安全性。这项拟议中的研究对公众健康很重要，因为它将提供确定安全有效的饮食策略所需的信息，以减少身体脂肪和改善整体健康。总体健康状况的改善预计将减少用于治疗肥胖和糖尿病所需的药物和保健的资金。