Depression, Adipocytokines and Metabolic Dysregulation in Black and White Women

黑人和白人女性的抑郁症、脂肪细胞因子和代谢失调

基本信息

批准号：
7821256
负责人：
SUSAN A EVERSON-ROSE
金额：
$ 18.86万
依托单位：
UNIVERSITY OF MINNESOTA
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：
2009-05-01 至 2012-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7821256
关键词：
Adipocytes Adipose tissue Affect African American Age Ancillary Study Anti-Inflammatory Agents Anti-inflammatory Antiatherogenic Area Autonomic nervous system Behavioral Biological Biological Assay Cardiovascular Diseases Cardiovascular system Caucasians Caucasoid Race Chronic stress Clinical Cohort Studies Communities Complex Cross-Sectional Studies Data Development Diabetes Mellitus Disadvantaged Dysthymic Disorder Emotions Epidemiologic Studies Event Freezing Funding Future Goals Inflammation Inflammatory Insulin Insulin Resistance Interview Knowledge Leptin Link Literature Major Depressive Disorder Mediating Menopausal Status Mental Depression Mental Health Metabolic Metabolic Marker Metabolic syndrome Metabolism Minority Groups Morbidity - disease rate Nervous System Physiology Obesity Parents Participant Pathway interactions Pattern Play Predisposition Prevalence Principal Investigator Process Psychosocial Factor Race Recording of previous events Regulation Relative (related person)Reporting Research Risk Risk Factors Role Sampling Serum Socioeconomic Status Specimen Stress Structure Testing Time Urine Woman Women&apos s Health adiponectin atherogenesis base cardiovascular disorder risk cardiovascular risk factor cohort cost depressive symptoms diabetes risk energy balance follow up assessment follow-up inflammatory marker insight interest middle age mortality novel programs public health relevance recurrent depression repository secretory protein socioeconomics

项目摘要

DESCRIPTION (provided by applicant): Important links between major depressive disorder/depressive symptoms and risk for cardiovascular disease (CVD) morbidity and mortality have been documented. Depression is associated with higher rates of obesity, metabolic syndrome (MetSyn) and diabetes and greater insulin resistance, indicators of metabolic dysregulation and known CVD risk factors. Depression likely contributes to CVD risk via metabolic dysregulation but precise mechanisms by which this occurs are unknown. Inflammation may play a key role. Atherogenesis, obesity, insulin resistance, diabetes, and MetSyn are known inflammatory processes, and depression has been linked with several inflammatory markers. Missing from the literature is systematic study of the association between depression and adipocytokines, secretory proteins released from adipocytes that play a critical role in the inflammatory process and are identified as highly significant in atherogenesis and metabolic dysregulation. Of specific interest in this application are adiponectin, an anti-inflammatory adipocytokine with insulin-sensitizing, anti-thrombotic and anti-atherogenic effects, and leptin, a pro-inflammatory adipocytokine intimately involved in regulation of metabolism, energy balance, and autonomic nervous system functioning. Both adiponectin and leptin are independently associated with increased risk of future cardiovascular events and increased subclinical cardiovascular disease. We will use an existing, well-characterized cohort of African-American and Caucasian women from the Study of Women's Health Across the Nation (SWAN) for our proposed research, which includes an observation cohort study (N=581) and a retrospective cohort study (N=266 without a history of CVD, diabetes or MetSyn) to examine both cross-sectional and longitudinal associations of lifetime history of depression and current depressive symptoms with adiponectin and leptin and changes in these adipocytokines over 5 years. Support is sought for assays of adiponectin and leptin from serum specimens stored in the NIA-existing SWAN Repository and for analysis and dissemination of our findings. By using an existing, well-characterized cohort with available serum specimens, we have a unique opportunity to test the novel hypotheses we are proposing in a highly cost-efficient manner. We believe this study will provide important data for future R01 efforts planned that will extend the principal investigators' research program to investigate more broadly the interrelationships of chronic stress, emotions and metabolic dysregulation. Findings have the potential to yield significant new insights regarding the impact of depression on metabolic dysregulation and cardiovascular risk in women. PUBLIC HEALTH RELEVANCE: The proposed study will examine whether depression is associated with the adipocytokines, adiponectin and leptin, bioactive molecules secreted by adipose tissue that play a critical role in atherogenesis and metabolic dysregulation, in a sample of middle-aged black and white women. Results of the study will provide significant new information on how depression affects risk for diabetes, metabolic syndrome, obesity and cardiovascular disease in women.

描述（由申请人提供）：已经记录了重大抑郁症/抑郁症状与心血管疾病（CVD）发病率和死亡率之间的重要联系。抑郁症与肥胖率更高，代谢综合征（METSYN）和糖尿病较高，胰岛素抵抗，代谢失调的指标和已知的CVD危险因素有关。抑郁症可能通过代谢失调导致CVD风险，但发生这种情况的精确机制尚不清楚。炎症可能起关键作用。动脉粥样硬化，肥胖症，胰岛素抵抗，糖尿病和梅西（Metsyn）是已知的炎症过程，并且抑郁症与几种炎症标记有关。文献中缺少的是对抑郁症与脂肪细胞之间的关联的系统研究，从脂肪细胞中释放出的分泌蛋白在炎症过程中起着至关重要的作用，并且在动脉粥样硬化和代谢失调中被认为非常重要。在此应用中特别感兴趣的是脂联素，一种抗炎脂肪细胞因子，具有胰岛素敏感性，抗栓性和抗动脉粥样硬化作用，以及瘦素，一种促炎性脂肪细胞因子，促炎性脂肪细胞因子密切涉及对代谢，能量平衡以及自动神经系统平衡的调节，以及自动神经系统平衡，以及功能。脂联素和瘦素都与增加未来心血管事件的风险和亚临床心血管疾病增加有关。我们将使用全国范围内的妇女健康研究（天鹅）进行现有的，良好的非裔美国人和高加索妇女的群体进行，其中包括一项观察队列研究（n = 581）和回顾性队列研究（n = 266，没有CVD史，糖尿病或Metsyn的病史）检查抑郁症的寿命和抑郁症状的横断面和纵向关联，以及与脂联素和瘦素的当前抑郁症状以及5年以来这些脂肪细胞因子的变化。寻求支持来自存储在NIA存在的天鹅存储库中的血清标本的脂联素和瘦素的测定，并分析和分析我们的发现。通过使用现有的，良好的人群和可用的血清标本，我们有一个独特的机会来测试我们以高度成本效益的方式提出的新型假设。我们认为，这项研究将为未来的R01努力提供重要的数据，该研究将扩展主要研究人员的研究计划，以更广泛地研究慢性压力，情绪和代谢失调的相互关系。发现有可能就抑郁症对女性代谢失调和心血管风险的影响产生重大新见解。公共卫生相关性：拟议的研究将检查抑郁症与脂肪组织分泌的脂肪细胞，脂联素和瘦素，生物活性分子是否相关，这些分子在中期黑白女性的样本中在动脉粥样硬化和代谢失调中起关键作用。该研究的结果将提供有关抑郁症如何影响女性糖尿病，代谢综合征，肥胖和心血管疾病的风险的重要新信息。