Role of Inflammatory Processes in Reward Network Alterations in Obesity

炎症过程在肥胖奖励网络改变中的作用

• 批准号: 9265841
• 负责人: ARPANA GUPTA
• 金额: $ 20.25万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9265841
• 关键词: Accounting; Address; Adjuvant Therapy; Adult; Adverse event; Algorithms; American; Amygdaloid structure; Anatomy; Anterior; Anti-Inflammatory Agents; Anti-inflammatory; Area; Award; Behavior; Behavior Therapy; Behavioral; Bioinformatics; Biological; Biological Markers; Brain; Brain region; Cardiovascular Diseases; Classification; Clinical; Clinical Data; Cognitive Therapy; Data; Data Analyses; Development; Diet; Diffusion; Disadvantaged; Disease; Eating; Eating Behavior; Educational workshop; Effectiveness; Emotions; Environment; Environmental Risk Factor; Epidemic; Feeding behaviors; Food Intake Regulation; Functional disorder; Gene Expression; Genes; Genetic; Genomics; Goals; Grant; Group Meetings; Health; Hypothalamic structure; Immune; Immune system; Individual; Inflammation Mediators; Inflammatory; Ingestion; Insula of Reil; Intervention; Investigation; Knowledge; Life Style; Link; Machine Learning; Magnetic Resonance Imaging; Mathematics; Measures; Mentors; Metadata; Modeling; Modification; Molecular; Molecular Profiling; Neurobiology; Neuronal Plasticity; Nucleus Accumbens; Obesity; Operative Surgical Procedures; Pathway interactions; Patients; Peripheral; Peripheral Blood Mononuclear Cell; Pharmacological Treatment; Plasma; Play; Process; Property; Psychology; Race; Research; Resistance; Rest; Rewards; Risk; Role; Satiation; Sex Characteristics; Signal Transduction; Socioeconomic Status; Source; Stress; Structure; Subgroup; Substance abuse problem; Sympathetic Nervous System; Techniques; Testing; Therapeutic Effect; Thinness; Training; Training and Infrastructure; Transcriptional Regulation; United States; Up-Regulation; Weight; addiction; bariatric surgery; base; behavior measurement; biological systems; biopsychosocial; brain shape; career; collaborative environment; cost effective; cytokine; emotion regulation; emotional eating; food addiction; food craving; global health; health disparity; hedonic; immunoregulation; indexing; meetings; metabolomics; mind control; multimodality; neurobiological mechanism; neuroimaging; neuroinflammation; obesity risk; obesity treatment; psychosocial; public health relevance; racial difference; social

 DESCRIPTION (provided by applicant): The main theme of this proposal is the identification of brain signatures associated with hedonic eating behaviors (HEB) and the role of inflammatory mediators in shaping these brain signatures. I will also evaluate the feasibility of using a targeted intervention (Cognitive Behavioral Therapy [CBT]) to counteract the hypothesized alterations within the extended reward network in this subgroup of obese subjects. This area of study is significant because increases in the hedonic component of food intake, which are no longer driven by homeostatic needs, are likely to play an important pathophysiological role in some obese individuals, but the mechanisms that bias the brain towards this alteration in ingestive behavior are incompletely understood. Here I will use inflammatory gene expression profiles to show that adverse experiences alter brain signatures within the extended reward network through the process of neuroinflammation. The proposal begins by characterizing brain signatures related to HEB. Then gene expression profiles as measured by peripheral blood mononuclear cells and plasma cytokines are identified and correlated with brain signatures and HEB. CBT will be used to investigate the therapeutic effect linked to strengthening inhibitory influences of prefrontal regions within the extended reward network, and reducing increased sympathetic nervous system modulation of the immune system, thereby offering a cost effective way of counteracting HEB. Advanced and sophisticated multivariate analytic techniques will be used to integrate the data from multiple neuroimaging sources, gene profiles, and behavioral data in order to determine the unique variance of adverse environmental factors in determining signatures associated with HEB. This may serve as a sensitive measure of central biomarkers in obesity related to HEB. A model that accounts for sex and race differences will increase the validity of the model, and will help identify disadvantaged groups who are at increased risk for obesity associated with HEB. I have a background in psychology and seek the following training goals from this award: (1) knowledge in the pathophysiology of obesity; (2) genomic analysis techniques including bioinformatics techniques; (3) knowledge and expertise in metabolomics data analysis; (4) specific expertise in diffusion tensor MRI analysis; (5) advanced data driven multivariate techniques using topological network and system biological analytical techniques (e.g. cluster and classification analysis); and (6) expertise in applying behavioral therapy to obesity. The work environment at the Center for Neurobiology of Stress provides an excellent infrastructure for training in neuro-genetic investigations of obesity. I will attend courses, workshops, and meetings in order to obtain a comprehensive understanding of the underlying biological sequelae of obesity. Regular individual and group meetings with mentors (Mayer [primary], Pisegna, Li, Cole, Labus, Naliboff [co-mentors]) have been set up. I plan to apply for a R03 grant by Year 3 and a R01 grant by Year 5. Long term, I plan to establish an independent research career in brain-gut interactions associated with health disparities in obesity.

 描述（由申请人提供）：该提案的主题是识别与享乐饮食行为（HEB）相关的大脑特征以及炎症介质在塑造这些大脑特征中的作用我还将评估使用有针对性的干预措施的可行性。 （认知行为疗法 [CBT]）来抵消肥胖受试者这一亚组中扩展奖励网络中所追求的改变，这一研究领域意义重大，因为食物摄入的享乐成分增加了，而这并没有增加。长期受稳态需求驱动，可能在一些肥胖个体中发挥重要的病理生理作用，但使大脑偏向这种摄入行为改变的机制尚不完全清楚，在这里我将使用炎症基因表达谱来表明不良经历会改变。该提案首先描述了与 HEB 相关的大脑特征，然后通过外周血单核细胞和血浆细胞因子测量基因表达谱，并将其与大脑特征相关联。 HEB 将用于研究与增强扩展奖励网络内的前额叶区域的抑制影响相关的治疗效果，并减少交感神经系统对免疫系统的调节，从而提供一种经济有效的方法来对抗高级 HEB。复杂的多变量分析技术将用于整合来自多个神经影像来源、基因谱和行为数据的数据，以确定与 HEB 相关的不良环境因素的独特方差，这可以作为中心生物标志物的敏感测量。在肥胖中考虑到性别和种族差异的模型将提高模型的有效性，并有助于识别与 HEB 相关的肥胖风险增加的弱势群体。我有心理学背景，并寻求以下培训目标。该奖项包括：(1) 肥胖病理生理学知识；(2) 基因组分析技术，包括生物信息学技术；(4) 扩散张量 MRI 分析方面的专业知识；数据驱动使用拓扑网络和系统生物分析技术的多变量技术（例如聚类和行为分类分析）；以及（6）将治疗应用于肥胖的专业知识压力神经生物学中心的工作环境为神经遗传学培训提供了良好的基础设施。我将参加课程、研讨会和会议，以便全面了解肥胖的潜在个人生物学后果。与导师（Mayer [primary]、Pisegna、Li、Cole、Labus、Naliboff）定期举行小组会议。 [共同导师]）已经成立，我计划申请。 第三年获得 R03 资助，第五年获得 R01 资助。从长远来看，我计划在与肥胖健康差异相关的脑肠相互作用方面建立独立的研究生涯。