Noninvasive Sensors of Metabolic Activity

描述（由申请人提供）：全球范围内持续的肥胖流行正在造成巨大的健康后果，包括2型糖尿病、癌症和心脏病的增加。 代谢综合征是一种恶性并发症，影响许多但不是所有的肥胖个体，并大大增加了患此类疾病的可能性。 虽然存在药物治疗，但治疗所有肥胖个体的成本将是令人望而却步的。 因此，一个关键的公共卫生需要的工具，提供代谢综合征的早期诊断和成本效益的治疗。 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。 能量和代谢的化学货币是三磷酸腺苷（ATP），由线粒体内的酶复合物产生。 初步工作表明，这种复合物产生谐波响应振荡电场。 该提案的重点是开发基于谐波发生光谱的传感器，该传感器检测线粒体中的代谢活动。 具体目标是：（1）开发检测体外细胞中线粒体复合物活性的传感器;（2）确定谐波光谱的哪些特征与特定酶复合物的活性相关;以及（3）评估检测肥胖患者代谢综合征的可行性。 这种方法将使最终开发的临床设备，可以检测代谢综合征的早期或监测休息和活跃的代谢。

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.