Influence of Fasting Status and Specimen Processing Time on Adipokine Levels

描述（由申请人提供）：介导肥胖和绝经后乳腺癌风险之间相关性的生物学途径尚未解决，尽管新数据表明脂肪因子水平的改变可能是肥胖-乳腺癌关系的部分基础。为了进一步阐明它们的作用，需要前瞻性收集血清进行大型流行病学研究，以评估肥胖生物标志物与癌症风险之间的关联。然而，目前关于脂肪因子和绝经后乳腺癌风险的研究结果是相互矛盾的，并且似乎各研究之间采血方案的主要差异可能导致了这种差异。因此，在进行新的研究之前，需要解决几个方法学/生物学问题。首先，考虑到它们在能量代谢中的作用，血清脂肪因子水平可能会随能量摄入而变化，但尚不清楚最后一餐和抽血之间的时间（禁食时间）如何影响脂肪因子测量，或者这些影响如何因体型而异。其次，血液处理的延迟可能会加速这些肽的降解;然而，目前尚不清楚脂肪因子的这种影响程度。为了研究能量摄入和样本处理时间对血清脂肪因子水平的影响，我们建议在45名绝经后妇女中测量空腹和非空腹样本以及立即和延迟处理的样本中的脂肪因子水平。研究人群已在洛克菲勒大学医院临床和转化科学中心（CCTS）用可用资金招募。研究受试者按顺序执行以下任务：（a）研究访视前一晚，指导参与者禁食，（B）第二天早上，女性到达CCTS并提供空腹血样，之后她们（c）食用标准研究早餐，最后，（d）在餐后1、3和6小时提供3次抽血。在抽血后立即、24小时和48小时处理血液样品以提取血清。我们正在申请资金在迈克尔·波拉克博士的实验室里分析这些血清样本中的脂肪因子水平。将使用重复测量的方差分析和配对t检验评价餐后采血与空腹采血以及不同处理时间的分析物值。这项研究的结果预计将告知未来的调查脂肪因子和女性生殖系统癌症，其中主要涉及绝经后妇女，虽然结果将适用于其他结果，并可能对其他群体，包括绝经前妇女和男子。因此，我们认为，了解空腹状态和血液处理时间在受控临床环境中的作用对于肥胖生物标志物和绝经后乳腺癌风险的大型流行病学研究的设计，分析和解释至关重要。 公共卫生相关性：项目叙述：该研究将在45名绝经后妇女的对照喂养试验中检查血液采集参数、空腹状态和处理时间是否影响脂肪因子的循环水平。描述餐后变化和处理时间对脂肪因子水平的影响将为脂肪因子和肥胖相关癌症的大型流行病学研究的设计、分析和解释提供信息。

DESCRIPTION (provided by applicant): The biological pathways that mediate the association between obesity and postmenopausal breast cancer risk are unresolved, although new data suggests that altered levels of adipokines may underlie, in part, the obesity- breast cancer relationship. To further clarify their role, large epidemiologic studies with prospectively-collected serum are needed to evaluate the associations between biomarkers of obesity and cancer risk. However, current findings on adipokines and risk of postmenopausal breast cancer are conflicting, and it is plausible that major differences in blood collection protocols across studies may have contributed to this variance. Therefore, before new studies can be conducted, several methodologic/biologic issues need to be addressed. First, given their role in energy metabolism, it is possible that serum adipokine levels may vary in response to energy intake but it is unknown how the time between last meal and blood draw (fasting time) influences adipokine measurements, or how these effects may differ by body size. Second, delays in blood processing may accelerate degradation of these peptides; however, the extent of this effect is currently not known for adipokines. To investigate the effect of energy intake and specimen processing time on serum adipokine levels, we propose to measure adipokine levels in fasting and non-fasting samples, as well as in samples processed immediately and with delays, in 45 postmenopausal women. The study population has been recruited with available funds at the Center for Clinical and Translational Science (CCTS) at the Rockefeller University Hospital. The study subjects performed the following tasks in sequential order: (a) the night before the study visit, participants were instructed to fast, (b) the following morning, women arrived at the CCTS and provided a fasting blood sample after which they (c) consumed a standard research breakfast and finally, (d) provided 3 blood draws at 1, 3, and 6 hours postprandial. Blood samples were processed immediately, 24 hours, and 48 hours after blood draw to extract serum. We are requesting funds to analyze adipokine levels in these serum samples at Dr. Michael Pollak's laboratory. Analyte values from postprandial blood draws compared to those from the fasting blood draw, as well as from different processing times, will be evaluated using analysis of variance tests for repeated measures and paired t-tests. Results of this study are expected to inform future investigations of adipokines and female reproductive cancers, which involve primarily postmenopausal women, although results will be applicable to other outcomes and possibly to other groups including premenopausal women and men. Thus, we believe that understanding the role of fasting status and blood processing time in a controlled clinical setting will be critical for the design, analyses, and interpretation of large epidemiologic studies of obesity biomarkers and postmenopausal breast cancer risk. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE The proposed study will examine whether blood collection parameters, fasting status and processing time, influence circulating levels of adipokines in a controlled feeding trial of 45 postmenopausal women. Description of the postprandial changes and effects of processing time to adipokine levels will inform the design, analysis, and interpretation of large epidemiologic studies of adipokines and obesity-related cancers.