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:
- 金额:$ 2.85万
- 依托单位:
- 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:
- 关键词:ATF2 geneAdipocytesAdipose tissueAdultAdverse effectsAnimalsApoptosisAttenuatedBlood VesselsBody WeightBody Weight decreasedBody fatCardiovascular DiseasesCell LineCell SeparationCell modelCellsChemicalsChemotactic FactorsChronic DiseaseCoculture TechniquesConditioned Culture MediaConjugated Linoleic AcidsCytokine GeneDataDiabetes MellitusDiseaseEndocrineExperimental ModelsExposure toFOS geneFatty AcidsFigs - dietaryFortified FoodGLUT4 geneGene ExpressionGene TargetingGenesGlucoseGoalsHealthHealth Care CostsHealthcareHumanHypertensionIL8 geneInflammationInflammatoryInflammatory ResponseInsulinInsulin ResistanceInterleukin-1IsomerismJUN geneKnowledgeLeadLinkLipolysisMAPK14 geneMAPK7 geneMaintenanceMeasuresMediatingMediator of activation proteinMetabolicMetabolismMitogen-Activated Protein KinasesModelingNF-kappa BNon-Insulin-Dependent Diabetes MellitusObesityObesity associated diseaseOutcomePTGS2 genePathway interactionsPeroxisome ProliferatorsPharmaceutical PreparationsPhosphotransferasesPopulationPrevalenceProductionProstaglandin-Endoperoxide SynthaseProstaglandinsProtein KinaseProteinsPublic HealthReportingResearchRiskRoleSafetySignal PathwaySignal TransductionSmall Interfering RNATestingTranscription Factor AP-1TriglyceridesWeight maintenance regimenWorkactivating transcription factor 3adiponectinattenuationbasecell typecytokinedietary supplementsdirect applicationimprovedinhibitor/antagonistinnovationinsulin signalinglipid biosynthesislipid metabolismmixed lineage kinase 3monocytenutritionprotein activationreceptorresponsestress-activated protein kinase 1upstream kinaseuptake
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):本研究的长期目标是确定安全有效的饮食策略,以减少肥胖及相关疾病的患病率。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,在动物和人类中已报道了一些不良副作用,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 CLA 治疗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,本提案的具体目标是 1) 确定 WAT 中的哪种细胞类型(即前脂肪细胞或脂肪细胞)是原代培养物中 10,12 CLA 介导的炎症、胰岛素抵抗和脱脂的主要介质。新分化的人类脂肪细胞,2) 以确定所涉及的具体机制。根据我的初步数据,目标#1 预计脂肪细胞是 10,12 CLA 诱导的炎症、胰岛素抵抗和脱脂的主要诱发因素。目标#2 预计 10,12 CLA 通过上游丝裂原激活蛋白激酶 (MAPK) 的激活来激活激活蛋白 (AP)-1,从而介导这些效应。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、胰岛素抵抗和脱脂中的作用。通过测量炎症基因表达、蛋白质激活以及脂肪细胞因子和前列腺素向介质中的分泌来检查炎症。胰岛素抵抗将通过测量胰岛素刺激的葡萄糖和脂肪酸的摄取来确定。这项研究的基本原理是,一旦我们了解 WAT 中的哪些细胞会触发 CLA 的炎症反应以及这种反应是如何发生的,就可以有效地评估其作为体重控制饮食方法的安全性。拟议的研究对公共卫生很重要,因为它将提供确定安全有效的饮食策略以减少身体脂肪和改善整体健康所需的信息。整体健康状况的改善预计将减少治疗肥胖和糖尿病所需的药物和医疗保健费用。
项目成果
期刊论文数量(0)
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Kristina Brooke Martinez-Guryn其他文献
Kristina Brooke Martinez-Guryn的其他文献
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