Noninvasive Sensors of Metabolic Activity

描述(申请人提供)：正在进行的全球肥胖流行正在造成巨大的健康后果，包括增加的2型糖尿病、癌症和心脏病。代谢综合征是一种有害的并发症，会影响许多(但不是所有)肥胖者，并极大地增加此类疾病的可能性。尽管存在药物治疗，但治疗所有肥胖者的成本将令人望而却步。因此，关键的公共卫生需求是提供代谢综合征早期诊断和成本效益治疗的工具。长期目标是开发检测人体代谢活动的技术，用于研究和临床应用。能量和新陈代谢的化学货币是三磷酸腺苷(ATP)，由线粒体内的酶复合体产生。初步工作表明，这种络合物会在振荡电场的作用下产生谐波。这项提议的重点是开发基于谐波产生光谱的传感器，这种传感器可以检测线粒体的代谢活动。其具体目标是：(1)开发传感器，在体外检测细胞中线粒体复合体的活性；(2)确定谐波光谱的哪些特征与特定酶复合体的活性相关；以及(3)评估检测肥胖患者代谢综合征的可行性。这种方法最终将使临床设备能够及早发现代谢综合征或监测静息和活跃的新陈代谢。

DESCRIPTION (provided by applicant): The ongoing worldwide obesity epidemic is creating enormous heath consequences, including increased type-2 diabetes, cancer, and heart disease. Metabolic syndrome is a pernicious complication that affects many, but not all, obese individuals and greatly increases the likelihood of such diseases. Although drug treatments exist, the cost to treat all obese individuals would be prohibitive. Therefore, a critical public health need exists for instruments that provide early diagnosis of metabolic syndrome and enable cost-effective treatment. The long-term goal is to develop technologies that detect metabolic activity in humans for research and clinical applications. The chemical currency of energy and metabolism is adenosine triphosphate (ATP), produced by enzyme complexes within mitochondria. Preliminary work suggests that such complexes generate harmonics in response to oscillatory electric fields. The focus of this proposal is to develop sensors, based on harmonic generation spectroscopy, which detect metabolic activity in mitochondria. The specific aims are to: (1) develop sensors that detect activity of mitochondrial complexes in cells in vitro; (2) determine which features of the harmonic spectra correlate with activity of specific enzyme complexes; and (3) assess the viability of detecting metabolic syndrome in obese patients. This approach will enable eventual development of clinical devices that can detect metabolic syndrome early or monitor resting and active metabolism.